Publications by authors named "Maryam S Daneshpour"

52 Publications

Diverse effect of MC4R risk alleles on obesity-related traits over a lifetime: Evidence from a well-designed cohort study.

Gene 2022 Jan 2;807:145950. Epub 2021 Sep 2.

Cellular, and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

This population-based longitudinal study is the first investigation that assesses the association of common MC4R SNPs with the obesity-related parameters over time and determines the effect of risk alleles during the three adulthood life periods (early, middle, and late) in a large Iranian cohort, a population with a unique genetic make-up that has been understudied and relatively unexplored. We obtained the genotype of 5370 unrelated adults who participated in the ongoing Tehran Cardiometabolic Genetic Study (TCGS) cohort project for the common MC4R SNPs. Linear regression and linear mixed model analyses were performed to examine the effect of MC4R polymorphisms on maximum BMI and other obesity-related factors over time. We recognized that several SNPs associated with the maximum BMI and the increased BMI, waist circumference, and waist-hip ratio across Iranian adults over a lifetime. Interestingly, we found that rs9954571-A has a yet unreported protective role against obesity-related factors, including BMI, waist circumference, waist-hip ratio, and triglyceride level. Additionally, a survey of the impact of the MC4R risk score throughout the adulthood life periods indicated that the MC4R risk score is influenced both the elevated BMI and waist circumference only during the early adulthood period. Our findings can expand our knowledge about the MC4R genetic variant's contributions to adulthood obesity and highlight the importance of evaluating the genetic components affecting obesity over a lifetime, which could be considered for obesity clinical screening and treatment.
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http://dx.doi.org/10.1016/j.gene.2021.145950DOI Listing
January 2022

Parental Transmission Plays the Major Role in High Aggregation of Type 2 Diabetes in Iranian Families: Tehran Lipid and Glucose Study.

Can J Diabetes 2021 Jun 1. Epub 2021 Jun 1.

Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Background: This study is the first to evaluate familial aggregation, heritability and inheritance mode of type 2 diabetes (T2D) in Tehran Lipid Glucose Study (TLGS) participants as a representative sample of the Iranian population.

Methods: From the ongoing family-based TLGS cohort, 13,741 individuals at least 20 years of age (mean ± standard deviation, 39.71±16.56) were assessed. After correcting family structures using genomic information from the Tehran Cardiometabolic Genetic Study, 2,594 constituent pedigrees were constructed. Familial aggregation was assessed based on genealogic index testing, familial intraclass correlation and positive family history. Family-based heritability was checked with 2 linear mixed models, including 2 different random components: the kinship matrix and the genomic relationship matrix. The mode of inheritance of T2D was investigated by complex segregation analysis (CSA).

Results: Familial aggregation of T2D was significant (p<0.05), and family-based heritability showed a high degree of genetic variation in T2D between individuals at 65% (standard error, 0.034). Within first-degree relatives (parent/offspring and siblings), the likelihood of a parental affect was higher than in siblings (odds ratio, 4.11 vs 1.65). Family history of T2D among first-degree relatives was more noteworthy than for second-degree relatives (odds ratio, 3.84 vs 0.59). CSA revealed that the polygenic model is best to illustrate the mode of inheritance of T2D for TLGS participants.

Conclusions: Our findings demonstrate that the heritability of T2D with polygenic mode in the Iranian population is higher than the global average. We also found that T2D is transmitted equally into siblings, with parental affect the leading risk factor. These data suggest that policymakers should change individual-level to family-level prevention.
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http://dx.doi.org/10.1016/j.jcjd.2021.05.009DOI Listing
June 2021

Genome-wide association study on blood pressure traits in the Iranian population suggests ZBED9 as a new locus for hypertension.

Sci Rep 2021 06 3;11(1):11699. Epub 2021 Jun 3.

Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

High blood pressure is the heritable risk factor for cardiovascular and kidney diseases. Genome-wide association studies(GWAS) on blood pressure traits increase our understanding of its underlying genetic basis. However, a large proportion of GWAS was conducted in Europeans, and some roadblocks deprive other populations to benefit from their results. Iranians population with a high degree of genomic specificity has not been represented in international databases to date, so to fill the gap, we explored the effects of 652,919 genomic variants on Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Hypertension (HTN) in 7694 Iranian adults aged 18 and over from Tehran Cardiometabolic Genetic Study (TCGS). We identified consistent signals on ZBED9 associated with HTN in the genome-wide borderline threshold after adjusting for different sets of environmental predictors. Moreover, strong signals on ABHD17C and suggestive signals on FBN1 were detected for DBP and SBP, respectively, while these signals were not consistent in different GWA analysis. Our finding on ZBED9 was confirmed for all BP traits by linkage analysis in an independent sample. We found significant associations with similar direction of effects and allele frequency of genetic variants on ZBED9 with DBP (genome-wide threshold) and HTN (nominal threshold) in GWAS summary data of UK Biobank. Although there is no strong evidence to support the function of ZBED9 in blood pressure regulation, it provides new insight into the pleiotropic effects of hypertension and other cardiovascular diseases.
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http://dx.doi.org/10.1038/s41598-021-90925-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175429PMC
June 2021

Kernel machine SNP set analysis finds the association of BUD13, ZPR1, and APOA5 variants with metabolic syndrome in Tehran Cardio-metabolic Genetics Study.

Sci Rep 2021 05 13;11(1):10305. Epub 2021 May 13.

Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, PO Box 19195-4763, Tehran, Iran.

Metabolic syndrome (MetS) is one of the most important risk factors for cardiovascular disease. The 11p23.3 chromosomal region plays a potential role in the pathogenesis of MetS. The present study aimed to assess the association between 18 single nucleotide polymorphisms (SNPs) located at the BUD13, ZPR1, and APOA5 genes with MetS in the Tehran Cardio-metabolic Genetics Study (TCGS). In 5421 MetS affected and non-affected participants, we analyzed the data using two models. The first model (MetS model) examined SNPs' association with MetS. The second model (HTg-MetS Model) examined the association of SNPs with MetS affection participants who had a high plasma triglyceride (TG). The four-gamete rules were used to make SNP sets from correlated nearby SNPs. The kernel machine regression models and single SNP regression evaluated the association between SNP sets and MetS. The kernel machine results showed two sets over three sets of correlated SNPs have a significant joint effect on both models (p < 0.0001). Also, single SNP regression results showed that the odds ratios (ORs) for both models are almost similar; however, the p-values had slightly higher significance levels in the HTg-MetS model. The strongest ORs in the HTg-MetS model belonged to the G allele in rs2266788 (MetS: OR = 1.3, p = 3.6 × 10; HTg-MetS: OR = 1.4, p = 2.3 × 10) and the T allele in rs651821 (MetS: OR = 1.3, p = 2.8 × 10; HTg-MetS: OR = 1.4, p = 3.6 × 10). In the present study, the kernel machine regression models could help assess the association between the BUD13, ZPR1, and APOA5 gene variants (11p23.3 region) with lipid-related traits in MetS and MetS affected with high TG.
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http://dx.doi.org/10.1038/s41598-021-89509-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119714PMC
May 2021

Interplay between SARS-CoV-2 and human long non-coding RNAs.

J Cell Mol Med 2021 06 9;25(12):5823-5827. Epub 2021 May 9.

Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

The long non-coding RNAs (lncRNAs) play a critical regulatory role in the host response to the viral infection. However, little is understood about the transcriptome architecture, especially lncRNAs pattern during the SARS-CoV-2 infection. In the present study, using publicly available RNA sequencing data of bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) samples from COVID-19 patients and healthy individuals, three interesting findings highlighted: (a) More than half of the interactions between lncRNAs-PCGs of BALF samples established by three trans-acting lncRNAs (HOTAIRM1, PVT1 and AL392172.1), which also exhibited the high affinity for binding to the SARS-CoV-2 genome, suggesting the major regulatory role of these lncRNAs during the SARS-CoV-2 infection. (b) lncRNAs of MALAT1 and NEAT1 are possibly contributed to the inflammation development in the SARS-CoV-2 infected cells. (c) In contrast to the 3' part of the SARS-CoV-2 genome, the 5' part can interact with many human lncRNAs. Therefore, the mRNA-based vaccines will not show any side effects because of the off-label interactions with the human lncRNAs. Overall, the putative functionalities of lncRNAs can be promising to design the non-coding RNA-based drugs and to inspect the efficiency of vaccines to overcome the current pandemic.
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http://dx.doi.org/10.1111/jcmm.16596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184717PMC
June 2021

Familial genetic and environmental risk profile and high blood pressure event: a prospective cohort of cardio-metabolic and genetic study.

Blood Press 2021 06 1;30(3):196-204. Epub 2021 Apr 1.

Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background And Aims: High blood pressure is the heritable risk factor for cardiovascular diseases. We investigated whether the presence of familial genetic and environmental risk factors are associated with increased risk of high blood pressure.

Methods: A total of 4,559 individuals from 401 families were included in this study. Familial aggregation analysis was carried out on systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI) and waist circumference (WC), and heritability was estimated for SBP and DBP. The association between familial risk factors and blood pressure traits including, incidence of hypertension, SBP and DBP was estimated separately using regression-based two-level Haseman-Elston (HE) method, with individual and familial BMI and WC as environmental exposures and familial genetic profile of known variants as genetic risk factors in 210 index families (≥2 hypertensive cases). Models were adjusted for the two nested sets of covariates.

Results: During a follow-up of 15 years, the SBP, DBP, BMI and WC were highly correlated in inter class of mother-offspring and intraclass of sister-sister with heritability of 30 and 25% for DBP and SBP, respectively. Among index families, those whose members with higher familial BMI or WC had significantly increased risk of hypertension and consistent, strong signals of rs2493134 () linked with SBP and DBP, rs976683 () linked with SBP and HTN, and epistasis of rs2021783 () and known genetic variants linked with all blood pressure traits.

Conclusions: Findings from this study show that familial genetic and environmental risk profile increase risk for high blood pressure beyond the effect of the individuals' own risk factors.
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http://dx.doi.org/10.1080/08037051.2021.1903807DOI Listing
June 2021

Chromosomal regions strongly associated with waist circumference and body mass index in metabolic syndrome in a family-based study.

Sci Rep 2021 03 16;11(1):6082. Epub 2021 Mar 16.

Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, PO Box, 19195-4763, Tehran, Iran.

Obesity is the most crucial phenotype in metabolic syndrome (MetS), and waist circumference (WC) and body mass index (BMI) are two common indexes to define obesity. It is an accepted fact that genetic and environmental interaction influence obesity and MetS. Microsatellites are a subcategory of tandem repeats with a length of 1 to 10 nucleotides. Tandem repeats make up repetitive genomic regions. Differences in the number of tandem repeats or their variation (alleles) result in microsatellite polymorphisms. Thus, we attempted to find microsatellite variation associated with WC and BMI in a family-based study. Twelve microsatellite markers were selected to investigate possible genes or chromosomal regions in 91 families with at least one affected MetS. The cut-off values for BMI and WC were considered 25 kg/m and 90 cm, respectively. In all members of the families, the strongest association was observed between the marker D11S1304 (allele 1) with both WC and BMI, independently, by the biallelic model in the family-based association test analysis (P < 0.05). Besides, when we compared high- and low-level groups in members with MetS, the markers D8S1743 and D11S1304 (allele 1) showed a strong association with WC (P = 0.0080) and BMI (P = 0.0074), respectively. When the simultaneous detection of the high WC and MetS status was used as a trait, the strongest association was observed with the marker D8S1743 (P = 0.0034). Moreover, when BMI with the high MetS status was used as a trait, the strongest association was observed with the marker D8S1743 (allele 4) (P = 0.0034). The obtained results showed a relationship between obesity and MetS with markers on the selected regions on chromosomes 8 and 11, and to a lesser degree, on chromosome 12.
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http://dx.doi.org/10.1038/s41598-021-85741-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966400PMC
March 2021

GWAS findings improved genomic prediction accuracy of lipid profile traits: Tehran Cardiometabolic Genetic Study.

Sci Rep 2021 Mar 11;11(1):5780. Epub 2021 Mar 11.

Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, POBox: 19195-4763, Tehran, Iran.

In recent decades, ongoing GWAS findings discovered novel therapeutic modifications such as whole-genome risk prediction in particular. Here, we proposed a method based on integrating the traditional genomic best linear unbiased prediction (gBLUP) approach with GWAS information to boost genetic prediction accuracy and gene-based heritability estimation. This study was conducted in the framework of the Tehran Cardio-metabolic Genetic study (TCGS) containing 14,827 individuals and 649,932 SNP markers. Five SNP subsets were selected based on GWAS results: top 1%, 5%, 10%, 50% significant SNPs, and reported associated SNPs in previous studies. Furthermore, we randomly selected subsets as large as every five subsets. Prediction accuracy has been investigated on lipid profile traits with a tenfold and 10-repeat cross-validation algorithm by the gBLUP method. Our results revealed that genetic prediction based on selected subsets of SNPs obtained from the dataset outperformed the subsets from previously reported SNPs. Selected SNPs' subsets acquired a more precise prediction than whole SNPs and much higher than randomly selected SNPs. Also, common SNPs with the most captured prediction accuracy in the selected sets caught the highest gene-based heritability. However, it is better to be mindful of the fact that a small number of SNPs obtained from GWAS results could capture a highly notable proportion of variance and prediction accuracy.
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http://dx.doi.org/10.1038/s41598-021-85203-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952573PMC
March 2021

Dietary diversity modifies the association between FTO polymorphisms and obesity phenotypes.

Int J Food Sci Nutr 2021 Nov 24;72(7):997-1007. Epub 2021 Feb 24.

Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

The current study aimed to evaluate the interaction of the dietary diversity score (DDS) and FTO polymorphisms concerning obesity phenotypes. The 4480 subjects of this cohort study were selected. The polymorphisms rs1121980, rs14211085 and rs8050136 were selected and genotyped. The weighted method was used to calculate the genetic risk score (GRS). Obesity marker changes were calculated. Those with minor allele carriers of rs1121980 had lower body mass index changes Q1: 1.58 ± 0.60 vs. Q4: 0.13 ± 0.59) and visceral adiposity index (VAI) (Q1: -0.00 ± 0.02 vs. Q4: -0.04 ± 0.02) when they had higher DDS (P interaction = 0.05). Carriers of the minor allele of rs8050136 had significant VAI change across DDS quartiles (Q1: -0.01 ± 0.02 vs. Q4: -0.02 ± 0.02, P interaction = 0.05). No significant interaction was found between the GRS and DDS on general obesity. The pattern of dietary diversity may have a mediatory role in improving obesity markers in subjects with a more genetic predisposition to adiposity.
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http://dx.doi.org/10.1080/09637486.2021.1890698DOI Listing
November 2021

GCKR common functional polymorphisms are associated with metabolic syndrome and its components: a 10-year retrospective cohort study in Iranian adults.

Diabetol Metab Syndr 2021 Feb 18;13(1):20. Epub 2021 Feb 18.

Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, POBox: 19195-4763, Tehran, Iran.

Background: Previous studies reported that common functional variants (rs780093, rs780094, and rs1260326) in the glucokinase regulator gene (GCKR) were associated with metabolic syndrome despite the simultaneous association with the favorable and unfavorable metabolic syndrome components. We decided to evaluate these findings in a cohort study with a large sample size of Iranian adult subjects, to our knowledge for the first time. We investigated the association of the GCKR variants with incident MetS in mean follow-up times for nearly 10 years.

Methods: Analysis of this retrospective cohort study was performed among 5666 participants of the Tehran Cardiometabolic Genetics Study (TCGS) at 19-88 years at baseline. Linear and logistic regression analyses were used to investigate the metabolic syndrome (JIS criteria) association and its components with rs780093, rs780094, and rs1260326 in an additive genetic model. Cox regression was carried out to peruse variants' association with the incidence of metabolic syndrome in the TCGS cohort study.

Results: In the current study, we have consistently replicated the association of the GCKR SNPs with higher triglyceride and lower fasting blood sugar levels (p < 0.05) in Iranian adults. The CT genotype of the variants was associated with lower HDL-C levels. The proportional Cox adjusted model regression resulted that TT carriers of rs780094, rs780093, and rs1260326 were associated with 20%, 23%, and 21% excess risk metabolic syndrome incidence, respectively (p < 0.05).

Conclusions: Elevated triglyceride levels had the strongest association with GCKR selected variants among the metabolic syndrome components. Despite the association of these variants with decreased fasting blood sugar levels, T alleles of the variants were associated with metabolic syndrome incidence; so whether individuals are T allele carriers of the common functional variants, they have a risk factor for the future incidence of metabolic syndrome.
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http://dx.doi.org/10.1186/s13098-021-00637-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890822PMC
February 2021

Low HDL concentration in rs2048327-G carriers can predispose men to develop coronary heart disease: Tehran Cardiometabolic genetic study (TCGS).

Gene 2021 Apr 11;778:145485. Epub 2021 Feb 11.

Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Recent genome-wide association studies (GWAS) highlighted the importance of genetic variations on SLC22A3 and MIA3 genes in developing coronary heart disease (CHD) among different ethnicities. However, the influence of these variations is not recognized within the Iranian population. Hence, in the present study, we aim to investigate two key single nucleotide polymorphisms (SNPs) on CHD incidence in this population. For this purpose, from Tehran Cardiometabolic Genetic Study (TCGS), 453 individuals with CHD were selected as a case and 453 individuals as a control that matched their age and gender. After quality control of two selected SNPs, rs2048327 (SLC22A3) and rs17465637 (MIA3), we used genotyps resulted from chip-typing technology and conducted the logistic regression analysis adjusted for non-genetic risk factors to detect the possible association of these SNPs with the CHD development. Our findings demonstrated the rs2048327-G and rs17465637-C can significantly increase the risk of CHD development about two times in only males and females, respectively. Interestingly, in the male carriers of the risk allele (G) of rs2048327, the low high-density lipoprotein (HDL) level can significantly predispose them to develop coronary heart disease in the future. According to our results, paying more attention to gender and genetic markers can help more efficient coronary heart disease screening and diagnosis.
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http://dx.doi.org/10.1016/j.gene.2021.145485DOI Listing
April 2021

SARS-CoV-2 infection susceptibility influenced by ACE2 genetic polymorphisms: insights from Tehran Cardio-Metabolic Genetic Study.

Sci Rep 2021 01 15;11(1):1529. Epub 2021 Jan 15.

Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, POBox: 19195-4763, Tehran, Iran.

The genetic variations among individuals are one of the notable factors determining disease severity and drug response. Nowadays, COVID-19 pandemic has been adversely affecting many aspects of human life. We used the Tehran Cardio-Metabolic Genetic Study (TCGS) data that is an ongoing genetic study including the whole-genome sequencing of 1200 individuals and chip genotyping of more than 15,000 participants. Here, the effect of ACE2 variations by focusing on the receptor-binding site of SARS-CoV-2 and ACE2 cleavage by TMPRSS2 protease were investigated through simulations study. After analyzing TCGS data, 570 genetic variations on the ACE2 gene, including single nucleotide polymorphisms (SNP) and insertion/deletion (INDEL) were detected. Interestingly, two observed missense variants, K26R and S331F, which only the first one was previously reported, can reduce the receptor affinity for the viral Spike protein. Moreover, our bioinformatics simulation of 3D structures and docking of proteins explains important details of ACE2-Spike and ACE2-TMPRSS2 interactions, especially the critical role of Arg652 of ACE2 for protease function of TMPRSS2 was uncovered. As our results show that the genetic variation of ACE2 can at least influence the affinity of this receptor to its partners, we need to consider the genetic variations on ACE2 as well as other genes in the pathways that contribute to the pathogenesis of COVID-19 for designing efficient drugs and vaccines.
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http://dx.doi.org/10.1038/s41598-020-80325-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810897PMC
January 2021

TCF7L2 polymorphisms, nut consumption, and the risk of metabolic syndrome: a prospective population based study.

Nutr Metab (Lond) 2021 Jan 12;18(1):10. Epub 2021 Jan 12.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: The aim of this study was to investigate whether two variants of the TCF7L2 (rs7903146 and rs12255372) modify the association between nut consumption and the risk of metabolic syndrome (MetS). Additionally, the modifying effect of weight change during follow-up on these associations was investigated.

Material And Methods: We prospectively studied 1423 participants of the Tehran Lipid and Glucose study aged 19-74 years who were followed-up for dietary assessment using a validated, semi-quantitative food frequency questionnaire. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) for MetS events. Genotyping was performed by Human Omni Express-24-v1-0 chip.

Results: Over a median 8.9 years of follow-up, 415 new cases of MetS were documented. The median nut consumption was 20.0 g/week (Interquartile Range (IQR): 8.6-38.9 g/week). Regarding the rs7903146 genotype, in carriers of T allele (CT + TT), highest tertile of nut consumption was associated with a reduced risk of MetS after adjusting for confounders (HR: 0.67 (0.50-0.91)). Regarding the rs12255372 genotype, highest versus lowest tertile of nut consumption in participants with T allele (GT + TT) resulted in 34% reduction of MetS risk after adjustment for confounders (HR: 0.66 (0.49-0.69)). After stratification by weigh change (< 7% or ≥ 7% weight gain), in individuals with ≥ 7% weight gain, highest tertile of nut consumption was associated with reduced risk of MetS among the risk allele of rs7903146. In the risk allele of rs12255372, among individuals with < 7% weight gain, third tertile of nuts intake reduced the risk of MetS, after adjustment for confounders.

Conclusion: Higher consumption of nuts may reduces the risk of MetS in T-risk allele of the TCF7L2 rs7903146 and rs12255372 variants and weight change may modify this association.
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http://dx.doi.org/10.1186/s12986-021-00542-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802263PMC
January 2021

The joint effect of PPARG upstream genetic variation in association with long-term persistent obesity: Tehran cardio-metabolic genetic study (TCGS).

Eat Weight Disord 2021 Oct 3;26(7):2325-2332. Epub 2021 Jan 3.

Cellular, and Molecular Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, 19195-4763, Tehran, Iran.

Purpose: This study is the first study that aims to assess the association between SNPs located at the PPARG gene with long term persistent obesity. In this cohort association study, all adult individuals who had at least three consecutive phases of BMI (at least nine years) in Tehran genetic Cardio-metabolic Study (TCGS) were included.

Methods: Individuals who always had 30 ≤ BMI < 35 and individuals who always had 20 < BMI ≤ 25 were assigned to the long-term persistent obese group and persistent normal weight group, respectively. Other individuals were excluded from the study. We used four gamete rules to make SNP sets from correlated nearby SNPs and kernel machine regression to analyze the association between SNP sets and persistent obesity or normal weight.

Results: The normal group consisted of 1547 individuals with the mean age of 40 years, and the obese group consisted of 1676 individuals with mean age of 48 years. Two groups had a significant difference between all measured clinical characteristics at entry time. The kernel machine result shows that nine correlated SNPs located upstream of PPARG have a significant joint effect on persistence obesity.

Conclusion: This is the first study on the association between PPARG variants with persistent obesity. Three of the nine associated markers were reported in previous GWAS studies to be associated with related diseases. For the studied markers in the PPARG gene, the Iranian allele frequency was near the American and European populations.

Level Iii: Case-control analytic study.
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http://dx.doi.org/10.1007/s40519-020-01063-7DOI Listing
October 2021

Role of Air Pollution and rs10830963 Polymorphism on the Incidence of Type 2 Diabetes: Tehran Cardiometabolic Genetic Study.

J Diabetes Res 2020 7;2020:2928618. Epub 2020 Sep 7.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Diabetes mellitus (DM) is considered one of the leading health issues that are egregiously threatening human life throughout the world. Several epidemiological studies have examined the relationship of a particular matter < 10 m (PM10) exposure and with type 2 diabetes mellitus (T2DM) prevalence and incidence. Accordingly, the current study is a study investigating the independent influence of air pollution (AP) and rs10830963 on the incidence of T2DM. A total number of 2428 adults over 20 years of age participated in a prospective cohort (TCGS) during a 9-year follow-up phase. The concentration of AP was measured, and the obtained values were considered the mean level in three previous years since the exposure concentration took the people living in that location. The COX regression model was employed to determine the influence of AP and rs10830963 on the incidence of T2DM in adjustment with covariate factors. Among the 392 T2DM, 230 cases (58.7%) were female diabetics, and 162 (41.3%) were male diabetics. According to the multivariable-adjusted model, exposure to PM10 (per 10 m/m3), associated with the risk of T2DM, although just a borderline ( = 0.07) was found in the multivariable model (HR; 1.50, 95% CI; 1-2.32). The rs10830963 was directly associated with the incidence of diabetes, and the GG genotype increased the T2DM rate by 113% (more than two times) (HR; 2.134, 95% CI; 1.42-3.21, ≤ 0.001) and GC increased it by 65% (HR; 1.65, 95% CI; 1.24-2.21, ≤ 0.001). Long-term exposure to PM10 was associated with an increased risk of diabetes. Thus, it is suggested that the individuals with variant rs10830963 genotypes fall within a group susceptible to an increased risk of T2DM arising from AP.
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http://dx.doi.org/10.1155/2020/2928618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502123PMC
July 2021

High genetic burden of type 2 diabetes can promote the high prevalence of disease: a longitudinal cohort study in Iran.

Sci Rep 2020 08 19;10(1):14006. Epub 2020 Aug 19.

Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Type 2 diabetes (T2D) is emerging as one of the serious public health issues in both developed and developing counties. Here, we surveyed the worldwide population differentiation in T2D-associated variants and assessed the genetic burden of the disease in an ongoing Tehran Cardio-Metabolic Genetic Study (TCGS) cohort represented the Iranian population. We found multiple SNPs that were significantly depleted or enriched in at least one of the five populations of 1,000 Genome Project (African, American, East Asian, European, and South Asian) as well as the Iranian population. Interestingly, TCF7L2, a well-known associated gene with T2D, harbors the highest number of enriched risk alleles almost in all populations except for East Asian, where this gene embraces the largest number of significantly depleted risk alleles. The polygenic risk score (PRS) of the enriched risk alleles was calculated for 1,867 diabetic and 2,855 non-diabetic participants in the TCGS cohort, interestingly demonstrating that the risk of developing T2D was almost two times higher in top PRS quintile compared with the lowest quintile after adjusting for other known risk factors.
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http://dx.doi.org/10.1038/s41598-020-70725-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438483PMC
August 2020

Genetic markers and continuity of healthy metabolic status: Tehran cardio-metabolic genetic study (TCGS).

Sci Rep 2020 08 12;10(1):13600. Epub 2020 Aug 12.

Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Science, P.O. Box: 19395-4763, Tehran, Iran.

Obese individuals can be categorized as "healthy obese" (MHO) and "unhealthy obese" (MUO) based on the presence or absence of metabolic abnormality. This study sets out to assess potential genetic causes behind persistence of healthy metabolic status in individuals categorized as "healthy obese". This study was conducted in the framework of the Tehran cardio-metabolic genetic study (TCGS). 766 MHO subjects at the start of the study followed up 15 years for occurrence of metabolic unhealthy status. These two groups (persistent MHO, MUO) were compared regarding the presence or absence of 16 single nucleotide polymorphisms (SNPs) identified as being associated with obesity phenotype in previous studies. We used logistic regression model for assessing the association between MHO/MUO with candidate SNPs. By the end of the follow up, 206 (27%) were categorized as the persistent MHO and 560 (73%) as MUO groups. Considering interaction effect between some SNP and sex, a sex stratification analysis was applied. When the analysis was performed by gender, rs1121980 associated with a decrease, and rs7903146 with an increase in the likelihood of persistent MHO individuals. Another analysis was separately performed on postmenopausal women from both groups; it showed that rs13107325 was associated with an increase in the likelihood of persistent MHO status in this subgroup of woman. In all cases, the markers had dominant inheritance. This findings suggest that the expression of some genetic markers are associated with persistence of healthy metabolic status, in female obese individuals.
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http://dx.doi.org/10.1038/s41598-020-70627-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423921PMC
August 2020

The interaction between dietary patterns and melanocortin-4 receptor polymorphisms in relation to obesity phenotypes.

Obes Res Clin Pract 2020 May - Jun;14(3):249-256. Epub 2020 May 20.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Introduction: Data shows that interactions between dietary factors and genetic variants can modulate the association of polymorphisms such as the Melanocortin-4 receptor (MC4R) gene with obesity. Considering the limited data available on this topic we aimed to investigate interactions between dietary patterns (DPs) and MC4R polymorphisms in relation to obesity phenotypes.

Methods: This cohort study was performed in the framework of Tehran Lipid and Glucose Study; for eligible participants in this study (n=3850), the median follow-up was 4 years. DPs were determined using factor analysis. The genotypes of polymorphisms (17782313rs and 12970134rs) were identified and their interaction with DPs were assessed in relation to incidence of obesity phenotypes including central obesity, general obesity and visceral adiposity dysfunction.

Results: The mean age of participants (62.5% females) were 37.0±13.7 years. Two main DPs (healthy and unhealthy) were extracted. C-allele carriers of rs17782313 in higher quartiles of the healthy DP score had a significant decrease in the incidence of general obesity, compared to those who had the TT genotype (HR=0.61, 95% CI=0.42-0.89, P interaction=0.01). For rs12970134 A-allele carriers, subjects in the second compared to the first quartile of the healthy DP score, had a significant decrease in the incidence of general obesity (HR=0.68, 95% CI=0.46-0.99). There were no significant interaction between DPs and MC4R variants in relation to other obesity phenotypes.

Conclusion: Our results indicate that the healthy DP could interact with rs17782313 in relation to incidence of general obesity.
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http://dx.doi.org/10.1016/j.orcp.2020.04.002DOI Listing
April 2021

Impact of secondhand smoke exposure in former smokers on their subsequent risk of coronary heart disease: evidence from the population-based cohort of the Tehran Lipid and Glucose Study.

Epidemiol Health 2020 8;42:e2020009. Epub 2020 Mar 8.

Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Objectives: Cigarette smoking is an established, strong, and modifiable risk factor for coronary heart disease (CHD). However, little research has investigated CHD risk in former smokers who continue to be exposed to others' cigarette smoke (former & secondhand smokers).

Methods: In the Tehran Lipid and Glucose Study, a prospective population-based cohort (n=20,069) was followed up for a median period of 14.6 years. A subset of 8,050 participants of 30 years of age and older was analyzed, with first CHD events as the study outcome. Participants were categorized as never, former, current, secondhand, and former & secondhand smokers. Data on smoking intensity (cigarette/d) were also collected. A Cox proportional hazards regression model was applied to estimate the risk of CHD, taking into account the main potential confounders.

Results: The mean age of participants was 46.10 ±11.38 years, and they experienced 1,118 first CHD events (with most CHD cases in former smokers) during the follow-up period. The risk of CHD was highest in current smokers, followed in order by former & secondhand, former, and secondhand smokers (hazard ratio [HR], 1.99; 95% confidence interval [CI], 1.65 to 2.39; HR, 1.55; 95% CI, 1.15 to 2.08; HR, 1.39; 95% CI, 1.12 to 1.72; HR, 1.27; 95% CI, 1.07 to 1.51, respectively), compared to never smokers. The risk of CHD increased with smoking intensity, which has been proposed as a preferable measure of smoking, indicating a dose-response pattern.

Conclusions: The elevated risk of CHD in former & secondhand smokers was a noteworthy finding, with possible implications for health policy; however, further research is needed.
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http://dx.doi.org/10.4178/epih.e2020009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285426PMC
June 2020

Associations of autozygosity with a broad range of human phenotypes.

Nat Commun 2019 10 31;10(1):4957. Epub 2019 Oct 31.

Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht University, Utrecht, 3584 CX, The Netherlands.

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F) for >1.4 million individuals, we show that F is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F are confirmed within full-sibling pairs, where the variation in F is independent of all environmental confounding.
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http://dx.doi.org/10.1038/s41467-019-12283-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823371PMC
October 2019

Presence of CC Genotype for rs17773430 Could Affect the Percentage of Excess Weight Loss 1 Year After Bariatric Surgery: Tehran Obesity Treatment Study (TOTS).

Obes Surg 2020 02;30(2):537-544

Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, PO Box 19195-4763, Tehran, Iran.

Background: Morbid obesity could last for a long period of life and increase the risk of morbidity as well as premature mortality. Although bariatric surgery benefits patients by quick weight loss, not all bariatric patients lose the same percentage of weight after a long time from surgery, which may be the result of diet, physical activity, and genetic components.

Objectives: In this study, we evaluated the association between the MC4R gene and both excess weight loss percentage (EWL%) and excess BMI loss percentage (EBMIL%) in a cohort of bariatric surgery patients after 6 and 12 months from surgery.

Methods: A total of 424 bariatric surgery patients who had participated in the Tehran Obesity Treatment Study and had weight measurements after 6 and 12 months from surgery were included in the study. Four SNPs in the MC4R gene were selected for evaluating the associations.

Results: We found that rs17773430 had a significant effect on both EWL% and EBMIL%, especially after 12 months of bariatric surgery. Furthermore, three other SNPs, rs17782313, rs476828, and rs11152213, did not show any significant association with EWL% and EBMIL%.

Conclusion: This study was the first to report on the association of rs17773430 with both EWL% and EBMIL% in a cohort of patients after bariatric surgery. We found that weight loss after surgery is influenced by genetic factors, and there were significant differences between the distribution of EWL% and EBMIL% in morbid obese bariatric patients who have two minor alleles of the rs17773430 and other SNPs.
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http://dx.doi.org/10.1007/s11695-019-04211-wDOI Listing
February 2020

Dietary patterns modify the association between fat mass and obesity-associated genetic variants and changes in obesity phenotypes.

Br J Nutr 2019 06 1;121(11):1247-1254. Epub 2019 Apr 1.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences,Tehran, 1985717413,Iran.

The present study investigated whether dietary patterns could interact with fat mass and obesity-associated (FTO) polymorphisms in relation to changes in BMI and waist circumference (WC) over 3⋅6 years of follow-up. Subjects were selected from participants of the Tehran Lipid and Glucose Study (n 4292, 43⋅2 % male). Dietary data were collected using a valid and reliable FFQ. Dietary patterns were determined using factor analysis. The genotypes of polymorphisms (rs1421085, rs1121980, rs17817449, rs8050136, rs9939973 and rs3751812) were determined. Genetic risk score (GRS) was calculated using the weighted method. Mean ages of men and women were 42·6 (sd 14) and 40⋅4 (sd 13) years, respectively. The healthy (e.g. vegetables and fruits) and the Western dietary patterns (WDP; e.g. soft drinks and fast foods) were extracted. In carriers of the risk alleles rs1121980, rs1421085, rs8050136, rs1781799 and rs3751812, BMI was approximately 2-fold higher in individuals in the higher quartile of WDP score, compared with the first quartile (P < 0⋅05). WC increased with increasing WDP score in carriers of the risk alleles rs1121980 and rs3751812, but not in individuals who did not carry any risk alleles. BMI and WC increased to a greater extent in the high GRS group while increasing quartiles of the WDP score, compared with the low GRS group (BMI change; Q1: 1⋅04 (se 0⋅34) v. Q4: 2⋅26 (se 0⋅36)) (WC change; Q1: 0⋅47 (se 0⋅32) v. Q4: 0⋅95 (se 0⋅34)) (P interaction < 0⋅05). These results suggest that adults with higher genetic predisposition to obesity are more susceptible to the harmful effects of adherence to the WDP, which emphasised the need to reduce the consumption of unhealthy foods for the prevention of obesity.
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http://dx.doi.org/10.1017/S0007114519000643DOI Listing
June 2019

Generality of genomic findings on blood pressure traits and its usefulness in precision medicine in diverse populations: A systematic review.

Clin Genet 2019 07 1;96(1):17-27. Epub 2019 Apr 1.

Department of Epidemiology, School of Public Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Remarkable findings from genome-wide association studies (GWAS) on blood pressure (BP) traits have made new insights for developing precision medicine toward more effective screening measures. However, generality of GWAS findings in diverse populations is hampered by some technical limitations. There is no comprehensive study to evaluate source(s) of the non-generality of GWAS results on BP traits, so to fill the gap, this systematic review study was carried out. Using MeSH terms, 1545 records were detected through searching in five databases and 49 relevant full-text articles were included in our review. Overall, 749 unique variants were reported, of those, majority of variants have been detected in Europeans and were associated to systolic and diastolic BP traits. Frequency of genetic variants with same position was low in European and non-European populations (n = 38). However, more than 200 (>25%) single nucleotide polymorphisms were found on same loci or linkage disequilibrium blocks (r ≥ 80%). Investigating for locus position and linkage disequilibrium of infrequent unique variants showed modest to high reproducibility of findings in Europeans that in some extent was generalizable in other populations. Beyond theoretical limitations, our study addressed other possible sources of non-generality of GWAS findings for BP traits in the same and different origins.
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http://dx.doi.org/10.1111/cge.13527DOI Listing
July 2019

Dietary Total Antioxidant Capacity and the Risk of Chronic Kidney Disease in Patients With Type 2 Diabetes: A Nested Case-Control Study in the Tehran Lipid Glucose Study.

J Ren Nutr 2019 09 29;29(5):394-398. Epub 2019 Jan 29.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Objective: Dietary total antioxidant capacity (DTAC) has been hypothesized as being involved in health promotion and disease prevention. However, data about the association of the DTAC (as estimated by ferric reducing antioxidant power) with diabetes chronic complications are scarce. Therefore, the aim of this study was to determine the associations between the DTAC and chronic kidney disease (CKD) risk in subjects with type 2 diabetic.

Methods: The present case-control study consisted of 210 (102 cases and 108 controls) patients with type 2 diabetic who were participants of the phase 5 Tehran Lipid and Glucose Study and were classified based on their CKD status. DTAC was estimated based on the ferric reducing antioxidant power of selected foods. Dietary intake, sociodemographic data, medical history, and anthropometric measurements were collected from participants using a validated questionnaire.

Results: The mean DTAC value, as well as total calorie intake, did not show significant differences between cases and controls.

Conclusion: No significant association was found between DTAC and CKD in patients with type 2 diabetic. Further studies are needed to confirm the effects of DTAC on the risk of CKD.
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http://dx.doi.org/10.1053/j.jrn.2018.11.008DOI Listing
September 2019

The interaction of cholesteryl ester transfer protein gene variations and diet on changes in serum lipid profiles.

Eur J Clin Nutr 2019 09 31;73(9):1291-1298. Epub 2019 Jan 31.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background/objectives: Gene-diet interactions may have an important role in the disparities between the lipid responses of individuals to diet. This study aimed to investigate whether polymorphisms (rs5882 and rs3764261) in the cholesteryl ester transfer protein (CETP) gene modify the association of diet with changes in serum lipid profiles.

Subjects/methods: A total of 4700 individuals aged ≥18 years were selected from among participants of the Tehran Lipid and Glucose Study. After 3.6 years of follow-up, changes in serum lipid profiles were evaluated. Usual dietary intake was assessed using a validated food frequency questionnaire. DNA samples were genotyped with HumanOmniExpress-24-v1-0 bead chips (containing 649,932 SNP loci).

Results: No significant interaction was found between CETP polymorphisms and dietary patterns in changing lipid profiles. Mean changes of total cholesterol (TC) decreased in higher quartiles of fish intake in A allele carriers (Q1:8.02, Q4:5.58, P = 0.01) compared to the CC genotype (Q1:3.65, Q4:8.93, P = 0.11) (P = 0.02). There are ascending trends of changes in triglyceride (TG) concentrations across quartiles of total fat, monounsaturated and saturated fat consumption in G allele carriers of rs5882 compared to the AA genotype. There was a declining trend for mean changes in TG concentrations across quartiles of carbohydrate intake in G allele carriers of rs5882 compared to the AA genotype (P = 0.01).

Conclusions: Our data demonstrated that minor allele carriers of rs5882 had a better TG value than AA homozygote individuals when consuming a low fat and high carbohydrate diet. Fish intake modifies the association of rs3764261with TC concentrations.
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http://dx.doi.org/10.1038/s41430-019-0397-xDOI Listing
September 2019

A novel association of rs13334070 in the RPGRIP1L gene with adiposity factors discovered by joint linkage and linkage disequilibrium analysis in Iranian pedigrees: Tehran Cardiometabolic Genetic Study (TCGS).

Genet Epidemiol 2019 04 30;43(3):342-351. Epub 2018 Dec 30.

Department of Cellular and Molecular, Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Understanding the genetic and metabolic bases of obesity is helpful in planning and developing health strategies. Therefore, the first family-based joint linkage and linkage disequilibrium study was conducted in Iranian pedigrees to assess the relationship between obesity and single-nucleotide polymorphisms (SNPs) located in the 16q12.2 region. In the present study, a total of 13,344 individuals were included, of whom 12,502 individuals were within 3,109 pedigrees and 842 were unrelated singletons. To investigate the relationship between obesity and genetic variants, a joint model of linkage and linkage disequilibrium was applied. Moreover, a sequence kernel association test (SKAT) was used to evaluate the association of the SNP set with body size and lipid profile measurements. The joint model showed that rs13334070, in the intron 4 of the RPGRIP1L gene, has a significant association with obesity. According to the 4-gamete rule, which is a procedure for constructing SNP sets by considering recombination occurrence between SNPs, this polymorphism has a high correlation with six nearby SNPs that make an SNP set. SKAT showed that this SNP set has a significant association with body size factors, but almost no association with most of the lipid profile measurements. In conclusion, from the result of this study, it might be reasonable to consider RPGRIP1L as an important gene whose variations could be associated with obesity risk factors.
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http://dx.doi.org/10.1002/gepi.22179DOI Listing
April 2019

Genetic Identification for Non-Communicable Disease: Findings from 20 Years of the Tehran Lipid and Glucose Study.

Int J Endocrinol Metab 2018 Oct 27;16(4 Suppl):e84744. Epub 2018 Oct 27.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Context: Tehran Lipid and Glucose Study (TLGS), a longitudinal family based cohort study, is the oldest and largest longitudinal family based study in Iran, aimed at investigating effects of environmental, social and biological factors on the health of Tehranians over time. Considering the importance of genetic studies in this aspect, here we present a summary of the important genetic findings, and the potentiality of their contributions to future related projects.

Evidence Acquisition: For all related studies during the past 20 years the search sources were all prominent search engines such as PubMed, Scopus, and Google Scholar with the most proper Medical Subject Headings (MeSH).

Results: This review summarizes associations of 6 binary phenotypes and 17 quantitative traits with genetic markers in 26 genes. Of the 47 genetic markers, studied most were related to cardio metabolic risk factors. Results of heritability and linkage analysis were also collected and the highest heritability was found to be related to HDL-C (0.5).

Conclusion: Considering the opportunity provided by large-scale cohort studies to investigate molecular effects of genetic variants on causality and different omics' data, genetic studies conducted on TLGS population have had a remarkable success in identifying genetic variants that facilitating a unique genetic database on Iranian populations. The results of genome wide association studies in this population are currently facilitating investigations to define the Iranian genetic differences with other population.
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http://dx.doi.org/10.5812/ijem.84744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289296PMC
October 2018

Dietary factors influence the association of cyclin D2 polymorphism rs11063069 with the risk of metabolic syndrome.

Nutr Res 2018 04 24;52:48-56. Epub 2017 Dec 24.

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

The relationship of CCND2 gene variation, rs11063069 with metabolic syndrome (MetS) modulates by dietary factors but enough data are not available on this issue. So, the hypothesis, which assumes that dietary factors modulate the relationship of CCND2 polymorphisms with the risk of MetS was investigated in our study. Subjects of this nested case-control study were selected from participants of the Tehran Lipid and Glucose Study. Each case (n=974) was pair-matched individually with a control by age, sex and the follow-up duration. Dietary patterns were determined using factor analysis. CCND2 rs11063069 was genotyped by the ARMS-polymerase chain reaction analysis. Two dietary patterns were extracted: the healthy dietary pattern (HDP) and the Western dietary pattern; among G allele carriers, being in the highest quartiles of HDP score decreased risk of MetS (OR, Q1:3.01 [1.95-6.15], Q4:0.88 [0.39-1.78], P trend=.001), compared with those in the lowest quartile. In addition, the consumption of some vegetables, red-yellow vegetable (tomatoes, squash and carrots) and fruits by G allele carriers could decrease the risk of high fasting plasma glucose (P interaction=.003), low HDL-C (P interaction=.03) and high blood pressure (P interaction=.01) respectively. No significant interaction was observed in this study between nutrients (macronutrients, zinc, magnesium and iron) and CCND2 rs11063069 in relation to MetS or its components in this study. Our findings showed that by promoting adherence to HDP and increasing intake of some vegetables and fruits, the risk of MetS or its components reduced in G allele carriers; these associations were not observed in the AA genotype group.
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http://dx.doi.org/10.1016/j.nutres.2017.12.006DOI Listing
April 2018

The relationship between MnSOD Val16Ala gene polymorphism and the level of serum total antioxidant capacity with the risk of chronic kidney disease in type 2 diabetic patients: a nested case-control study in the Tehran lipid glucose study.

Nutr Metab (Lond) 2018 11;15:25. Epub 2018 Apr 11.

6Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Several studies have shown significant associations between manganese superoxide dismutase (MnSOD) Val16Ala polymorphism and diabetic complications, but this association has not been explored in relation with chronic kidney disease (CKD) in Type 2 diabetes mellitus (T2DM) patients. Total antioxidant capacity (TAC) level changes in diabetic condition and may play important role in onset or progression of the disease and its complications. The present study investigated the association of MnSOD Val16Ala polymorphism and serum TAC with the risk of CKD in T2DM patients.

Methods: This nested case-control study included 280 type 2 diabetic patients with CKD and 280 age, sex and diabetes duration-matched control subjects selected from the participants of the Tehran Lipid and Glucose Study. MnSOD val16Ala (rs4880) SNP was genotyped by the Tetra-Primer ARMS-polymerase chain reaction analysis. Serum TAC was measured using ferric-reducing antioxidant power assay. Statistical analysis was performed using STATA statistical package v.12.0 or SPSS (Version 22.0).

Results: The Ala allele of the MnSOD Val16Ala polymorphism was associated with a lower risk of CKD (odds ratio (OR), 0.55; 95% confidence interval (CI), 0.36-0.84;  = 0.006). Median serum TAC in CKD group was 920 μmol/L and was significantly lower ( < 0.001) compared to the control group (1045 μmol/L). Using an adjusted conditional logistic regression, we didn't observe any significant interaction between MnSOD Val16Ala SNP with quartiles of serum TAC in relation to CKD.

Conclusion: A significant association was found between the MnSOD Val16Ala polymorphism and CKD, but this association is not affected by serum TAC level in T2DM patients.
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http://dx.doi.org/10.1186/s12986-018-0264-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896129PMC
April 2018

Familial aggregation and linkage analysis with covariates for metabolic syndrome risk factors.

Gene 2018 Jun 14;659:118-122. Epub 2018 Mar 14.

Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Mechanisms of metabolic syndrome (MetS) causation are complex, genetic and environmental factors are important factors for the pathogenesis of MetS In this study, we aimed to evaluate familial and genetic influences on metabolic syndrome risk factor and also assess association between FTO (rs1558902 and rs7202116) and CETP(rs1864163) genes' single nucleotide polymorphisms (SNP) with low HDL_C in the Tehran Lipid and Glucose Study (TLGS).

Materials And Methods: The design was a cross-sectional study of 1776 members of 227 randomly-ascertained families. Selected families contained at least one affected metabolic syndrome and at least two members of the family had suffered a loss of HDL_C according to ATP III criteria. In this study, after confirming the familial aggregation with intra-trait correlation coefficients (ICC) of Metabolic syndrome (MetS) and the quantitative lipid traits, the genetic linkage analysis of HDL_C was performed using conditional logistic method with adjusted sex and age.

Results: The results of the aggregation analysis revealed a higher correlation between siblings than between parent-offspring pairs representing the role of genetic factors in MetS. In addition, the conditional logistic model with covariates showed that the linkage results between HDL_C and three marker, rs1558902, rs7202116 and rs1864163 were significant.

Conclusions: In summary, a high risk of MetS was found in siblings confirming the genetic influences of metabolic syndrome risk factor. Moreover, the power to detect linkage increases in the one parameter conditional logistic model regarding the use of age and sex as covariates.
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http://dx.doi.org/10.1016/j.gene.2018.03.033DOI Listing
June 2018
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