Publications by authors named "Reza Najafipour"

42 Publications

SARS-CoV-2 outbreak in Iran; the dynamics of the epidemic and evidence on two independent introductions.

Transbound Emerg Dis 2021 Apr 9. Epub 2021 Apr 9.

Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.

The SARS-CoV-2 virus has been rapidly spreading globally since December 2019, triggering a pandemic, soon after its emergence. While Iran was among the first countries confronted with rapid spread of virus in February 2020, no real-time SARS-CoV-2 whole-genome tracking in early phase of outbreak was performed in the country. To address this issue, we provided 50 whole-genome sequences of viral isolates ascertained from different geographical locations in Iran during March-July 2020. The corresponding analysis on origins, transmission dynamics and genetic diversity of SARS-CoV-2 virus, represented at least two introductions of the virus into the country, constructing two major clusters defined as B.4 and B.1*. The first entry of the virus might have occurred around 29 December 2019, as suggested by the time to the most recent common ancestor, followed by a rapid community transmission that led to dominancy of B.4 lineage in early epidemic till the end of June. Gradually, reduction in dominancy of B.4 occurred possibly as a result of other entries of the virus, followed by surge of B.1* lineages, as of mid-May. Remarkably, variation tracking of the virus indicated the increase in frequency of D614G mutation, along with B.1* lineages, which showed continuity till October 2020. The increase in frequency of D614G mutation and B.1* lineages from mid-May onward predicts a rapid viral transmission that may push the country into a critical health situation followed by a considerable change in composition of viral lineages circulating in the country.
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http://dx.doi.org/10.1111/tbed.14104DOI Listing
April 2021

Underexpression of family and their promoter hypermethylation in infertile men: A case-control study.

Int J Reprod Biomed 2021 Jan 25;19(1):23-34. Epub 2021 Jan 25.

Research Institute for Prevention of Non-Communicable Diseases, Cellular and Molecular Research Centre, Qazvin University of Medical Sciences, Qazvin, Iran.

Background: Post-transcriptional microRNAs (miRNAs) have a impotrant pattern in the spermatogenesis process.

Objective: Study of the expression and methylation of family in sperm samples of infertile men.

Materials And Methods: In this case-control study, we recruited 74 infertile men (with asthenozoospermia, teratozoospermia, asthenoteratozoospermia, and oligoasthenoteratozoospermia) and 30 control samles. Methylation-specific PCR (MSP) method was used for methylation evaluation of promoter. By Real time PCR (qRT-PCR) method,we showed downregulation of in the sperm samples of infertile men and compared it to their fertile counterparts.

Results: There was significant underexperssion, in in oligoasthenoteratospermic samples (p = 0.0001, F = 2.9). About the methylation pattern, infertile men showed high frequency of methylation in the promoter of in comparison to controls (60.8% vs 23.3%), the highest amount of methylation was observed in oligoasthenoteratospermia samples (81.2%).

Conclusion: In this study, low expression and high methylation of were observed in infertile men in compared to control samples, which can be one of the causes of defective spermatogenesis.
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http://dx.doi.org/10.18502/ijrm.v19i1.8177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851476PMC
January 2021

Clinical and Genetic Characteristics of Splicing Variant in CYP27A1 in an Iranian Family with Cerebrotendinous Xanthomatosis.

Iran Biomed J 2021 03 1;25(2):132-9. Epub 2021 Mar 1.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Cerebrotendinous xanthomatosis (CTX) is a rare congenital lipid-storage disorder, leading to a progressive multisystem disease. CTX with autosomal recessive inheritance is caused by a defect in the CYP27A1 gene. Chronic diarrhea, tendon xanthomas, neurologic impairment, and bilateral cataracts are common symptoms of the disease.

Methods: Three affected siblings with an initial diagnosis of non-syndromic intellectual disability were recruited for further molecular investigations. To identify the possible genetic cause(s), whole exome sequencing was performed on the proband. Sanger sequencing was applied to confirm the final variant. The clinical and molecular genetic features of the three siblings from the new CTX family and other patients with the same mutations, as previously reported, were analyzed. The CYP27A1 gene was also studied for the number of pathogenic variants and their location.

Results: We found a homozygous splicing mutation, NM_000784: exon6: c.1184+1G>A, in CYP27A1 gene, which was confirmed by Sanger sequencing. Among the detected pathogenic variants, the splice site mutation had the highest prevalence, and the mutations were mostly found in exon 4.

Conclusion: This study is the first to report the c.1184+1G>A mutation in Iran. Our findings highlight the other feature of the disease, which is the lack of relationship between phenotype and genotype. Due to nonspecific symptoms and delay in diagnosis, CYP27A1 genetic analysis should be the definitive method for CTX diagnosis.
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http://dx.doi.org/10.29252/ibj.25.2.132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921520PMC
March 2021

Comprehensive genotype-phenotype correlation in AP-4 deficiency syndrome; Adding data from a large cohort of Iranian patients.

Clin Genet 2021 Jan 14;99(1):187-192. Epub 2020 Sep 14.

Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.

Mutations in adaptor protein complex-4 (AP-4) genes have first been identified in 2009, causing a phenotype termed as AP-4 deficiency syndrome. Since then several patients with overlapping phenotypes, comprised of intellectual disability (ID) and spastic tetraplegia have been reported. To delineate the genotype-phenotype correlation of the AP-4 deficiency syndrome, we add the data from 30 affected individuals from 12 out of 640 Iranian families with ID in whom we detected disease-causing variants in AP-4 complex subunits, using next-generation sequencing. Furthermore, by comparing genotype-phenotype findings of those affected individuals with previously reported patients, we further refine the genotype-phenotype correlation in this syndrome. The most frequent reported clinical findings in the 101 cases consist of ID and/or global developmental delay (97%), speech disorders (92.1%), inability to walk (90.1%), spasticity (77.2%), and microcephaly (75.2%). Spastic tetraplegia has been reported in 72.3% of the investigated patients. The major brain imaging findings are abnormal corpus callosum morphology (63.4%) followed by ventriculomegaly (44.5%). Our result might suggest the AP-4 deficiency syndrome as a major differential diagnostic for unknown hereditary neurodegenerative disorders.
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http://dx.doi.org/10.1111/cge.13845DOI Listing
January 2021

Natural Selection at the NHLH2 Core Promoter Exceptionally Long CA-Repeat in Human and Disease-Only Genotypes in Late-Onset Neurocognitive Disorder.

Gerontology 2020 2;66(5):514-522. Epub 2020 Sep 2.

Iranian Research Center on Aging, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran,

Background: Approximately 2% of the human core promoter short tandem repeats (STRs) reach lengths of ≥6 repeats, which may in part be a result of adaptive evolutionary processes and natural selection. A single-exon transcript of the human nescient helix loop helix 2 (NHLH2) gene is flanked by the longest CA-repeat detected in a human protein-coding gene core promoter (Ensembl transcript ID: ENST00000369506.1). NHLH2 is involved in several biological and pathological pathways, such as motivated exercise, obesity, and diabetes.

Methods: The allele and genotype distribution of the NHLH2 CA-repeat were investigated by sequencing in 655 Iranian subjects, consisting of late-onset neurocognitive disorder (NCD) as a clinical entity (n = 290) and matched controls (n = 365). The evolutionary trend of the CA-repeat was also studied across vertebrates.

Results: The allele range was between 9 and 25 repeats in the NCD cases, and 12 and 24 repeats in the controls. At the frequency of 0.56, the 21-repeat allele was the predominant allele in the controls. While the 21-repeat was also the predominant allele in the NCD patients, we detected significant decline of the frequency (p < 0.0001) and homozygosity (p < 0.006) of this allele in this group. Furthermore, 12 genotypes were detected across 16 patients (5.5% of the entire NCD sample) and not in the controls (disease-only genotypes; p < 0.0003), consisting of at least one extreme allele. The extreme alleles were at 9, 12, 13, 18, and 19 repeats (extreme short end), and 23, 24, and 25 repeats (extreme long end), and their frequencies ranged between 0.001 and 0.04. The frequency of the 21-repeat allele significantly dropped to 0.09 in the disease-only genotype compartment (p < 0.0001). Evolutionarily, while the maximum length of the NHLH2 CA-repeat was 11 repeats in non-primates, this CA-repeat was ≥14 repeats in primates and reached maximum length in human.

Conclusion: We propose a novel locus for late-onset NCD at the NHLH2 core promoter exceptionally long CA-STR and natural selection at this locus. Furthermore, there was indication of genotypes at this locus that unambiguously linked to late-onset NCD. This is the first instance of natural selection in favor of a predominantly abundant STR allele in human and its differential distribution in late-onset NCD.
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http://dx.doi.org/10.1159/000509471DOI Listing
September 2020

Expression and Methylation Pattern of hsa-miR-34 Family in Sperm Samples of Infertile Men.

Reprod Sci 2020 01 1;27(1):301-308. Epub 2020 Jan 1.

Cellular and Molecular Research Centre, Qazvin University of Medical Sciences, P.O. Box: 341197-5981, Qazvin, Iran.

Production of high-quality spermatozoa is necessary for male fertility. In this regard, post-mitotic stage in spermatogenesis is very important which posttranscriptional microRNAs (miRNAs) playing a key role at this stage. In this research, we evaluated the expression and methylation of hsa-miR-34 family in sperm samples of infertile men. We recruited 102 infertile men (asthenozoospermia, teratozoospermia, asthenoteratozoospermia, and oligoasthenoteratozoospermia) and 52 fertile men as control. The expression of hsa-miR-34a,b,c was determined by quantitative real-time PCR (qRT-PCR) technique. Methylation of hsa-miR-34b,c promoter was evaluated by methylation-specific PCR (MS-PCR) method. Our data indicated under-expression of three miRNAs (hsa-miR-34a,b,c) in the sperm samples of infertile men in compared to their fertile counterparts. The highest rate of expression reduction was observed in hsa-miR-34c-5p and in oligoasthenoteratospermic patients (P = 0.011, F = 4.01). The results revealed that the frequency of methylation of the promoter region of hsa-miR-34b,c in infertile men was higher than that of fertile men (82.4% versus 23.3%), and the highest frequency of methylation was observed in patients with asthenoteratospermia (92.9%) and oligoasthenoteratospermia (93.8%). In conclusion, our results indicated lower expression of hsa-miR-34a,b,c and hypermethylation of hsa-miR-34b,c promoter in sperm samples of infertile men. Aberrant under-expression of these miRNAs could be duo to the hypermethylation of the promoter region and indicative of a defect in spermatogenesis.
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http://dx.doi.org/10.1007/s43032-019-00025-4DOI Listing
January 2020

A novel PTC mutation in the BTB domain of KLHL7 gene in two patients with Bohring-Opitz syndrome-like features.

Eur J Med Genet 2020 Apr 15;63(4):103849. Epub 2020 Jan 15.

Cellular and Molecular Research Centre, Qazvin University of Medical Sciences, Qazvin, Iran. Electronic address:

The bric-a-brac, tramtrack and broad complex (BTB) superfamily of conserved proteins are involved in ubiquitin-proteasome system that contains the Kelch-like (KLHL) gene family. Kelch-like family member 7 (KLHL7), one of the KLHL gene family, consists of one BTB/POZ domain, one BACK domain and five or six Kelch motifs. Numerous variants in KLHL7 gene domains have been reported with Crisponi syndrome/cold-induced sweating syndrome type 1 (CS/CISS1)-like features and retinitis pigmentosa 42, and have recently been identified as causing Bohring-Opitz syndrome (BOS)-like features. We report two siblings with BOS-like phenotype with healthy parents and living in Qazvin province (Central Iran). We performed whole-exome sequencing (WES) on the older patient and Sanger sequencing was carried out for validation of potential causative variants in the close family. A novel homozygous frameshift mutation, p.(Phe83Leufs*3), was identified in the BTB domain of KLHL7 that caused a premature translation-termination codon (PTC) in the two siblings with severe developmental delay, microcephaly, facial dysmorphism, peripheral retinal and optic disc atrophy and cardiac septal defects. Our findings are in agreement with the clinical spectrum of KLHL7 mutations, which are associated with BOS-like features that reports for first time in our population.
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http://dx.doi.org/10.1016/j.ejmg.2020.103849DOI Listing
April 2020

Distinct genetic variation and heterogeneity of the Iranian population.

PLoS Genet 2019 09 24;15(9):e1008385. Epub 2019 Sep 24.

Cologne Center for Genomics, University of Cologne, Cologne, Germany.

Iran, despite its size, geographic location and past cultural influence, has largely been a blind spot for human population genetic studies. With only sparse genetic information on the Iranian population available, we pursued its genome-wide and geographic characterization based on 1021 samples from eleven ethnic groups. We show that Iranians, while close to neighboring populations, present distinct genetic variation consistent with long-standing genetic continuity, harbor high heterogeneity and different levels of consanguinity, fall apart into a cluster of similar groups and several admixed ones and have experienced numerous language adoption events in the past. Our findings render Iran an important source for human genetic variation in Western and Central Asia, will guide adequate study sampling and assist the interpretation of putative disease-implicated genetic variation. Given Iran's internal genetic heterogeneity, future studies will have to consider ethnic affiliations and possible admixture.
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http://dx.doi.org/10.1371/journal.pgen.1008385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759149PMC
September 2019

Iranome: A catalog of genomic variations in the Iranian population.

Hum Mutat 2019 11 17;40(11):1968-1984. Epub 2019 Aug 17.

Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.

Considering the application of human genome variation databases in precision medicine, population-specific genome projects are continuously being developed. However, the Middle Eastern population is underrepresented in current databases. Accordingly, we established Iranome database (www.iranome.com) by performing whole exome sequencing on 800 individuals from eight major Iranian ethnic groups representing the second largest population of Middle East. We identified 1,575,702 variants of which 308,311 were novel (19.6%). Also, by presenting higher frequency for 37,384 novel or known rare variants, Iranome database can improve the power of molecular diagnosis. Moreover, attainable clinical information makes this database a good resource for classifying pathogenicity of rare variants. Principal components analysis indicated that, apart from Iranian-Baluchs, Iranian-Turkmen, and Iranian-Persian Gulf Islanders, who form their own clusters, rest of the population were genetically linked, forming a super-population. Furthermore, only 0.6% of novel variants showed counterparts in "Greater Middle East Variome Project", emphasizing the value of Iranome at national level by releasing a comprehensive catalog of Iranian genomic variations and also filling another gap in the catalog of human genome variations at international level. We introduce Iranome as a resource which may also be applicable in other countries located in neighboring regions historically called Greater Iran (Persia).
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http://dx.doi.org/10.1002/humu.23880DOI Listing
November 2019

Effect of inbreeding on intellectual disability revisited by trio sequencing.

Clin Genet 2019 01 19;95(1):151-159. Epub 2018 Nov 19.

Max Planck Institute for Molecular Genetics, Berlin, Germany.

In outbred Western populations, most individuals with intellectual disability (ID) are sporadic cases, dominant de novo mutations (DNM) are frequent, and autosomal recessive ID (ARID) is very rare. Because of the high rate of parental consanguinity, which raises the risk for ARID and other recessive disorders, the prevalence of ID is significantly higher in near- and middle-east countries. Indeed, homozygosity mapping and sequencing in consanguineous families have already identified a plethora of ARID genes, but because of the design of these studies, DNMs could not be systematically assessed, and the proportion of cases that are potentially preventable by avoiding consanguineous marriages or through carrier testing is hitherto unknown. This prompted us to perform whole-exome sequencing in 100 sporadic ID patients from Iran and their healthy consanguineous parents. In 61 patients, we identified apparently causative changes in known ID genes. Of these, 44 were homozygous recessive and 17 dominant DNMs. Assuming that the DNM rate is stable, these results suggest that parental consanguinity raises the ID risk about 3.6-fold, and about 4.1 to 4.25-fold for children of first-cousin unions. These results do not rhyme with recent opinions that consanguinity-related health risks are generally small and have been "overstated" in the past.
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http://dx.doi.org/10.1111/cge.13463DOI Listing
January 2019

Prevalence and Distribution of Radix Paramolaris in the Mandibular First and Second Molars of an Iranian Population.

J Int Soc Prev Community Dent 2018 May-Jun;8(3):240-244. Epub 2018 Apr 26.

Endodontology Research Center, School of Dentistry, Kerman University of Medical Sciences and Health Services, Kerman, Iran.

Objectives: Inability to find supernumerary roots is one of the most important reasons for root canal therapy failures in molar teeth. This research aimed to determine the incidence and distribution of radix paramolaris in permanent mandibular molars of the population of Kerman. Iran over 2016-2017.

Materials And Methods: This study was performed on a collection of 500 extracted permanent mandibular first and second molars selected by random from different dental centers in Kerman without recording the sex and age of the patients as inclusion criteria. The incidence of additional mesiobuccal root (radix paramolaris), the average root length and morphology of this root was carefully determined following the Calberson and Alexanderson classification pattern.

Results: The incidence of radix paramolaris was 1.2% in mandibular first molars (0.8% Type A and 0.4% Type B) and 0.8% in mandibular second molars (0.4% Type A and 0.4% Type B) of this population. Fischer's Exact test showed that the difference in frequency of the radix paramolaris between first and second mandibular molars of this population was not statistically significant (two-sided = 0.0001). The average length for radix paramolaris was 13.05 mms in mandibular first and second molars in this study.

Conclusion: Radix paramolaris was found more frequently in mandibular first molars than in mandibular second molars in this sample of 500 mandibular molars. The rate of 1.2% in first molars seems to be higher than reported rates in European or Caucasian populations where the prevalence is typically <0.5%.
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http://dx.doi.org/10.4103/jispcd.JISPCD_58_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985681PMC
April 2018

Association of rs1057035polymorphism in microRNA biogenesis pathway gene (DICER1) with azoospermia among Iranian population.

Genes Genomics 2018 01 29;40(1):17-24. Epub 2017 Aug 29.

Biology-Genetic Department, School of Basic Science, Arak University, Arak, Iran.

Since genes involved in microRNA biogenesis pathways have a main role in impaired spermatogenesis, in this research, we evaluated different genotypes frequency of seven single-nucleotide polymorphisms in DICER1 and DROSHA genes. Different genotypes frequency of DICER1 (rs12323635, rs1057035, rs13078 and rs3742330) and DROSHA (rs10719, rs642321 and rs2291102) were determined by sequencing method in 385 infertile men and 120 fertile controls. It was found that CC genotype (P = 0.000) and C allele (P = 0.0) of rs1057035 T > C polymorphism were associated with idiopathic male infertility (azoospermia). Gene expression study in blood and testis samples was done by real time PCR technique. Our results showed significant under expression of DICER1 gene in blood and testis tissues of azoospermic samples (P < 0.05), but we did not observed significant difference in expression ratio between infertile men with and without C allele of rs1057035 SNP (P > 0.05). The results of this study showed that among the studied variants, only one of them in DICER1 might be associated with azoospermia, but additional studies needs in different populations and ethnics.
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http://dx.doi.org/10.1007/s13258-017-0605-9DOI Listing
January 2018

Association of -604G/A and -501A/C Ghrelin and Obestatin Prepropeptide Gene Polymorphisms with Polycystic Ovary Syndrome.

Biochem Genet 2018 Apr 11;56(1-2):116-127. Epub 2017 Dec 11.

Department of Clinical Biochemistry and Genetics, Cellular and Molecular Research Center, Faculty of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.

Ghrelin hormone has an important role in a wide range of metabolic and non-metabolic processes. Polymorphisms of ghrelin gene could be associated with a large number of diseases. The aim of this study was to evaluate the association of -604G/A and -501A/C polymorphisms in ghrelin and obestatin prepropeptide gene (GHRL) with polycystic ovary syndrome (PCOS) in a sample of Iranian women. One hundred and fifty-two women with PCOS and 162 age-matched apparently healthy women as control group were enrolled in this study. The study subjects were genotyped for polymorphisms in the ghrelin gene using polymerase chain reaction-restriction fragment length polymorphism-based methods. Biochemical parameters, serum prolactin, luteinizing hormone, follicle stimulating hormone, estradiol, and testosterone were estimated by chemiluminescence assay. Serum lipids and lipoproteins were determined by standard enzymatic methods. The association between the risk of PCOS and ghrelin gene polymorphisms was examined using Multivariate analysis. The frequency of the -604G/A and -501A/C polymorphisms was not statistically different between patients and the control group of women (p = 0.12 and p = 0.21, respectively). A significantly higher level of LDL-C was found in the wild-type AA genotype compared with CC genotype of -501A/C polymorphism (p = 0.02). Our findings indicate that neither -604G/A and nor -501A/C polymorphisms of ghrelin gene are associated with PCOS, but suggest a relation between the presence of polymorphic allele of -501A/C polymorphism and LDL-C level in a sample of Iranian women.
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http://dx.doi.org/10.1007/s10528-017-9834-5DOI Listing
April 2018

Major Components of Metabolic Parameters and Nutritional Intakes in Different Genotypes of Adiponectin +276 G>T Gene Polymorphism in Non-Diabetes and Non-Alcoholic Iranian Fatty Liver Patients.

Avicenna J Med Biotechnol 2017 Jul-Sep;9(3):155-161

Cellular and Molecular Research Center of Qazvin University of Medical Science, Qazvin, Iran.

Background: Genetic and environmental factors are both involved in the etiology of Non-Alcoholic Fatty Liver Disease (NAFLD). Among the genetic factors, certain polymorphisms of adiponectin gene are associated with NAFLD. In the current study, we investigated the association between metabolic parameters with different genotypes of adiponectin +276 G>T polymorphism among the Iranian NAFLD patients, and the effect of nutritional intake with development of NAFLD.

Methods: In this study, 75 patients with NAFLD and 76 healthy individuals were enrolled. Dietary intakes were assessed using a semi-quantitative Food-Frequency Questionnaire (FFQ). Body Mass Index (BMI) and Waist to Hip Ratio (WHR) were calculated. Biochemical assays including FSG (Fasting Serum Glucose), liver enzymes, lipid profiles, Malondialdehyde, insulin resistance and Total Antioxidant Capacity (TAC) were measured after 12 fasting. Gene polymorphism study was done by using of sequencing method.

Results: Although, T allele frequency was more prevalent in patients with NAFLD than control, adiponectin +276 G>T polymorphism was not associated with risk of NAFLD. Among the metabolic parameters, TAC in TT genotype was significantly lower 1.44(0.69 to 2.81) p>0.05, AST in GT, GG genotypes, and ALT in all three genotypes were higher in NAFLD patients in compared to healthy subjects (p<0.05). Patients with GT genotype have significantly lower fat consumption and vitamin E intake as compared to control group with the same genotype (p<0.05).

Conclusion: In this study, we showed the association of different genotypes of +276 G>T polymorphism in adiponectin gene with some metabolic parameters.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501145PMC
July 2017

An association study between CHEK2 gene mutations and susceptibility to breast cancer.

Comp Clin Path 2017 8;26(4):837-845. Epub 2017 Apr 8.

Department of Medical Genetics, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar-Abbas, Iran.

CHEK2 gene is known as a tumor suppressor gene in breast cancer (BC), which plays a role in DNA repair. The germ line mutations in CEHK2 have been associated with different types of cancer. The present study was aimed at studying the association between CHEK2 mutations and BC. Peripheral blood was collected from patients into a test tube containing EDTA, and DNA was extracted from blood samples. Then, we analyzed mutations including 1100delc, IVS2+1>A, del5395bp, and I157T within CHEK2 gene in patients with BC and 100 normal healthy controls according to PCR-RFLP, allelic specific PCR, and multiplex-PCR. Although IVS2+1G>A mutation within CHEK2 gene was found in two BC patients, other defined mutants were not detected. For the first time, we identified CHEK2 IVS2+1G>A mutation, one out of four different CHEK2 alterations in two Iranian BC patients (2%). Also, our results showed that CHEK2 1100elC, del5395bp, and I157T mutations are not associated with genetic susceptibility for BC among Iranian population.
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http://dx.doi.org/10.1007/s00580-017-2455-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489611PMC
April 2017

Blockade of fast A-type and TEA-sensitive potassium channels provide an antiparkinsonian effect in a 6-OHDA animal model.

Neurosciences (Riyadh) 2017 01;22(1):44-50

Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran.

Objective: To evaluate the effect of K+ channels inhibitors in treatment of parkinson`s disease (PD).

Methods: This prospective comparative study was conducted in the Qazvin University of Medical Sciences, Iran, from April 2015 to January 2016. Male rats (n=37) received intraperitoneal doses of TEA (2 and 5 mg/kg) or 4-AP (0.5 and 1 mg/kg) twice-daily, before a stereotactic injection of 6-hydroxydopamine (6-OHDA) for the following 7 days. The 6-OHDA was injected into right medial forebrain bundle (MFB) of the rat brains. Development and severity of PD were assessed using the apomorphine-induced rotational test, the elevated body swing test and rotarod tests. Concentration of malondialdehyde (MDA), a marker of oxidative stress, was measured in rat sera.

Results: Tetraethylammonium and 4-AP significantly reduced the number of apomorphine-induced rotations and improved motor learning in the rotarod test at both doses. Administration of 4-AP and TEA together was more effective than single administration of either agent. Malondialdehyde measurement showed that pretreatment with TEA could not prevent 6-OHDA-induced oxidative stress.

Conclusion: Our results showed that pretreatment with TEA and 4-AP has a neuroprotective effect against 6-OHDA in dopaminergic neurons in the substantia nigra.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726837PMC
http://dx.doi.org/10.17712/nsj.2017.1.20160266DOI Listing
January 2017

The Effects of Kainic Acid-Induced Seizure on Gene Expression of Brain Neurotransmitter Receptors in Mice Using RT PCR Array.

Basic Clin Neurosci 2016 Oct;7(4):291-298

Department of Pharmacology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.

Introduction: Kainic acid (KA) induces neuropathological changes in specific regions of the mouse hippocampus comparable to changes seen in patients with chronic temporal lobe epilepsy (TLE). According to different studies, the expression of a number of genes are altered in the adult rat hippocampus after status epilepticus (SE) induced by KA. This study aimed to quantitatively evaluate changes in the gene expression of brain neurotransmitter receptors one week after administration of kainic acid in the mouse hippocampus.

Methods: We used 12 BALB/c mice in this study and randomly divided them into 2 groups. To both groups, saline (IP) was administered for 7 days, and on the last day, KA (10 mg/kg, IP) was injected 30 minutes after administration of saline. Subsequently, behavioural changes were observed in mice. Then, in one group (1 day group), 2 hours and in another group (7 days group), 7 days after KA administration, the hippocampus tissue of mice was removed and used for gene expression analyses. Total brain RNA was isolated and reversely transcribed. We performed qPCR using RT Profiler PCR Array Mouse Neurotransmitter Receptors and Regulators (QIAGEN) containing primers for 84 genes. In this regard, we selected 50 related genes for KA model.

Results: Our results showed significant changes in the gene expression of GABA subunits receptors, including α1-α3, α5, α6, β2, β3, γ1, ρ, and rho1-2 on day 7 compared with the day 1.

Conclusion: Expression of both inhibitory and excitatory receptors changed after one week. Further studies are needed to find more molecular changes in the gene expression of brain neurotransmitter receptors and regulators over longer periods of time in KA models using RT PCR array.
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http://dx.doi.org/10.15412/J.BCN.03070402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102558PMC
October 2016

The effects of quercetin on the gene expression of the GABA receptor α5 subunit gene in a mouse model of kainic acid-induced seizure.

J Physiol Sci 2017 Mar 14;67(2):339-343. Epub 2016 Oct 14.

Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran.

The flavonoid quercetin has recently been reported to have neuroprotective effects, and the role of the gamma-aminobutyric acid A alpha 5 subunit (GABA α5) receptor has been determined in some nervous system disorders. The aim of this study was to identify the molecular mechanism of the effect of quercetin administered at anticonvulsive doses on the expression of the GABA α5 receptor gene in kainic acid (KA)-induced seizures in mice. The experimental animals were divided into four groups: control, KA, and KA + quercetin at 50 or 100 mg/kg, respectively. The results showed a dose-dependent reduction in the behavioral seizure score with quercetin pre-treatment in the KA mouse model. Two hours after the end of the 7-day treatment regimen, expression of the GABA α5 receptor gene in the hippocampus was found to be increased in the KA group, but this increase was reduced in the KA + quercetin 50 or 100 mg/kg treatment groups. These results suggest that expression of the GABA α5 receptor could be a mechanism for reducing seizure severity or may be a marker of seizure severity. Further studies are necessary to clarify quercetin's mechanism of action and the relation of GABA α5 receptor gene expression to seizure severity.
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http://dx.doi.org/10.1007/s12576-016-0497-5DOI Listing
March 2017

High prevalence of plasmid-mediated quinolone resistance determinants in Enterobacter cloacae isolated from hospitals of the Qazvin, Alborz, and Tehran provinces, Iran.

Rev Soc Bras Med Trop 2016 May-Jun;49(3):286-91

Celular e Molecular Research Center, Qazvin Universidade de Ciências Médicas, Qazvin, Iran.

Introduction: Plasmid-mediated quinolone resistance (PMQR) is a growing clinical concern worldwide. The main aims of this study were to detect qnr-encoding genes and to evaluate the clonal relatedness of qnr-positive Enterobacter cloacae isolates.

Methods: A total of 116 E. cloacae isolates that were not susceptible to quinolone were obtained from seven hospitals in Tehran, five hospitals in Qazvin, and two hospitals in Karaj (Iran). Bacterial identification was performed using standard laboratory methods and API 20E strips. Quinolone resistance was determined using the Kirby-Bauer disk diffusion method according to the Clinical Laboratory Standards Institute (CLSI) guidelines. PCR and sequencing were employed to detect qnrA, qnrB, and qnrS genes, and clonal relatedness was assessed using the enterobacterial repetitive intergenic consensus (ERIC)-PCR method.

Results: In total, 45 (38.8%) and 71 (61.2%) of isolates showed high- and low-level quinolone resistance, respectively, and qnr-encoding genes were detected in 70 (60.3%) of them. qnrB1 [45 (38.8%) isolates] was the most commonly detected gene, followed by qnrS1 [28 (24.1%) isolates] and qnrB4 [18 (15.5%) isolates] either alone or in combination with other genes. The results of the ERIC-PCR revealed that 53 (75.7%) qnr-positive isolates were genetically unrelated.

Conclusions: This study describes, for the first time, the high prevalence of the qnrB1, qnrS1, and qnrB4 genes among E. cloacae isolates in Iran. The detection of qnr genes emphasizes the need for establishing tactful policies associated with infection control measures in hospital settings in Iran.
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http://dx.doi.org/10.1590/0037-8682-0454-2015DOI Listing
March 2017

Dissemination of Pseudomonas aeruginosa producing bla IMP-1 and bla VIM-1 in Qazvin and Alborz educational hospitals, Iran.

Iran J Microbiol 2015 Dec;7(6):302-9

Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran.

Background And Objectives: Pseudomonas aeruginosa is a frequent opportunistic pathogen in health care associated infections that is highly resistant to the majority of β-lactams. The aims of this study were to access the antimicrobial susceptibility pattern of P. aeruginosa isolated from educational hospitals of Qazvin and Alborz provinces, to determine the prevalence of metallo-β-lactamase (MBL) among carbapenem non-susceptible isolates by combined disk (CD) method, and to detect the bla IMP, bla VIM, bla SIM, bla GIM, bla SPM and bla NDM-1-MBL genes.

Materials And Methods: In this cross-sectional study, 300 P. aeruginosa isolates were collected from different clinical specimens in two provinces of Qazvin and Alborz hospitals, Iran. After identification of isolates by standard laboratory methods, antimicrobial susceptibility was done against 17 antibiotics according to clinical and laboratory standards institute (CLSI) guideline. CD method was carried out for detection of MBLs and the presence of bla IMP, bla VIM, bla SIM, bla GIM, bla NDM-1 and bla SPM-genes was further assessed by PCR and sequencing methods.

Results: In this study, 107 (35.66%) isolates were non-susceptible to imipenem and/or meropenem among those 56 (52.3%) isolates were metallo-β-lactamase producer. Twenty-four of 56 (42.85%) MBL-positive isolates were confirmed to be positive for MBL-encoding genes in which 14 (25%) and 10 (17.85%) isolates carried bla IMP-1 and bla VIM-1 genes either alone or in combination. Three (5.35%) isolates carried bla IMP and bla VIM genes, simultaneously.

Conclusion: Considering the moderate prevalence and clinical importance of MBL-producing isolates, rapid identification and use of appropriate infection control (IC) measures are necessary to prevent further spread of infections by these resistant organisms.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752683PMC
December 2015

Investigation of FIH-1 and SOCS3 expression in KRAS mutant and wild-type patients with colorectal cancer.

Tumour Biol 2016 Jul 9;37(7):8841-8. Epub 2016 Jan 9.

Departments of Medical Informatics, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran.

Colorectal cancer (CRC) is a multistep process based on the accumulation of somatic mutations in genes such as APC and KRAS. Data on the presence of mutations in KRAS gene in CRC and its relationship with clinicopathological parameters and expression of genes involved in tumor progression are scarce. We unbiasedly examined the KRAS status in samples from 99 patients and its correlation with clinicopathological parameters such as age, sex, tumor location, lymph node metastasis, tumor stage, tumor grade, and vascular invasion. Consistent with reports of other researchers, 38.4 % of our samples harbored KRAS mutation in their genomes with preferential mutation in codon 12 (89.4 %). Nevertheless, unlike previous reports, we were not able to correlate KRAS status with clinicopathological parameters (P > 0.05) except for vascular invasion. Patients with KRAS mutation have more vascular invasion compared with patient having wild-type KRAS. Next, we investigated the expression of two tumor suppressor genes, factor-inhibiting hypoxia-inducible factor 1 (FIH-1) and suppressor of cytokine signaling (SOCS3), in both KRAS mutant and wild-type groups and looked for any correlation between their expression and clinicopathological parameters. Although the expression of both genes was not regular, none of the clinicopathological parameters were associated with the expressions of FIH-1 and SOCS3 at mRNA level (P > 0.05). However, decline in FIH-1 expression at protein level in KRAS mutant group was correlated with stage IV and grade 2 of tumor (P ≤ 0.05). Our results demonstrated that there is no or low correlation between KRAS status, FIH-1, and SOCS3 expression with epidemiologic and clinicpathological characteristics in CRC.
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http://dx.doi.org/10.1007/s13277-015-4723-1DOI Listing
July 2016

Comparison of Protamine 1 to Protamine 2 mRNA Ratio and YBX2 gene mRNA Content in Testicular Tissue of Fertile and Azoospermic Men.

Int J Fertil Steril 2015 Oct-Dec;9(3):338-45. Epub 2015 Oct 31.

Cellular and Molecular Research Centre, Qazvin University of Medical Sciences, Qazvin, Iran.

Background: Although aberrant protamine (PRM) ratios have been observed in infertile men, the mechanisms that implicit the uncoupling of PRM1 and PRM2 expression remain unclear. To uncover these mechanisms, in this observational study we have compared the PRM1/PRM2 mRNA ratio and mRNA contents of two regulatory factors of these genes.

Materials And Methods: In this experimental study, sampling was performed by a multi-step method from 50 non-obstructive azoospermic and 12 normal men. After RNA extraction and cDNA synthesis, real-time quantitative polymerase chain reaction (RT- QPCR) was used to analyze the PRM1, PRM2, Y box binding protein 2 (YBX2) and JmjC-containing histone demethylase 2a (JHDM2A) genes in testicular biopsies of the studied samples.

Results: The PRM1/PRM2 mRNA ratio differed significantly among studied groups, namely 0.21 ± 0.13 in azoospermic samples and -0.8 ± 0.22 in fertile samples. The amount of PRM2 mRNA, significantly reduced in azoospermic patients. Azoospermic men exhibited significant under expression of YBX2 gene compared to controls (P<0.001). mRNA content of this gene showed a positive correlation with PRM mRNA ratio (R=0.6, P=0.007). JHDM2A gene expression ratio did not show any significant difference between the studied groups (P=0.3). We also observed no correlation between JHDM2A mRNA content and the PRM mRNA ratio (R=0.2, P=0.3).

Conclusion: We found significant correlation between the aberrant PRM ratio (PRM2 under expression) and lower YBX2 mRNA content in testicular biopsies of azoospermic men compared to controls, which suggested that downregulation of the YBX2 gene might be involved in PRM2 under expression. These molecules could be useful biomarkers for predicting male infertility.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4671373PMC
http://dx.doi.org/10.22074/ijfs.2015.4549DOI Listing
December 2015

Mutations of the phenylalanine hydroxylase gene in Iranian patients with phenylketonuria.

Springerplus 2015 23;4:542. Epub 2015 Sep 23.

Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran.

Phenylketonuria (PKU) is an autosomal recessive disease which results from mutations in the phenylalanine hydroxylase (PAH) gene. The aim of this study was the identification of sixteen different mutations in Iranian patients with hyperphenylalaninemia. The mutations were detected during the characterization of PAH genotypes of 39 PKU patients from Qazvin and Zanjan provinces of Iran. PAH mutations have been analyzed by PCR and direct sequencing of PCR products of the promoter region and all 13 exons of PAH gene, including the splicing sites. A mutation detection rate of 74.3 % was realized. Two mutations were found at high frequencies: R176X (10.25 %) and p.P281L (10.25 %). The frequencies of the other mutations were: IVS2+5G>A (2.56 %), IVS2+5G>C (2.56 %), p.L48S (2.56 %), p.R243Q (2.56 %), p.R252Q (5.12 %), p.R261Q (7.69 %), p.R261X (5.12 %), p.E280K (2.56 %), p.I283N (2.56 %), IVS9+5G>A (2.56 %), IVS9+1G>A (1.28 %), IVS11+1G>C (1.28 %), p.C357R (1.28 %), c.632delC (2.56 %). The present results confirm the high heterogeneity of the PAH locus and contribute to information about the distribution and frequency of PKU mutations in the Iranian population.
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http://dx.doi.org/10.1186/s40064-015-1309-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579200PMC
September 2015

Mutations in the histamine N-methyltransferase gene, HNMT, are associated with nonsyndromic autosomal recessive intellectual disability.

Hum Mol Genet 2015 Oct 23;24(20):5697-710. Epub 2015 Jul 23.

Molecular Neuropsychiatry and Development (MiND) Lab, The Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada M5T 1R8, Department of Psychiatry, University of Toronto, Toronto, ON, Canada M5T 1R8 and Institute of Medical Science, University of Toronto, Toronto, ON, Canada M5S 1A8

Histamine (HA) acts as a neurotransmitter in the brain, which participates in the regulation of many biological processes including inflammation, gastric acid secretion and neuromodulation. The enzyme histamine N-methyltransferase (HNMT) inactivates HA by transferring a methyl group from S-adenosyl-l-methionine to HA, and is the only well-known pathway for termination of neurotransmission actions of HA in mammalian central nervous system. We performed autozygosity mapping followed by targeted exome sequencing and identified two homozygous HNMT alterations, p.Gly60Asp and p.Leu208Pro, in patients affected with nonsyndromic autosomal recessive intellectual disability from two unrelated consanguineous families of Turkish and Kurdish ancestry, respectively. We verified the complete absence of a functional HNMT in patients using in vitro toxicology assay. Using mutant and wild-type DNA constructs as well as in silico protein modeling, we confirmed that p.Gly60Asp disrupts the enzymatic activity of the protein, and that p.Leu208Pro results in reduced protein stability, resulting in decreased HA inactivation. Our results highlight the importance of inclusion of HNMT for genetic testing of individuals presenting with intellectual disability.
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http://dx.doi.org/10.1093/hmg/ddv286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581600PMC
October 2015

Evaluation of mRNA Contents of YBX2 and JHDM2A Genes on Testicular Tissues of Azoospermic Men with Different Classes of Spermatogenesis.

Cell J 2015 8;17(1):121-8. Epub 2015 Apr 8.

Department of Medical Genetics, Qazvin University of Medical Sciences, Qazvin, Iran.

Objective: Animal model studies have shown that MSY2 and JHDM2A genes have an important role in spermatogenesis process and fertility of male mice. But the potential role of these genes in human spermatogenesis and fertility is not known yet. Therefore, we evaluated expression ratios of these genes in testis tissues of men with normal and impaired spermatogenesis.

Materials And Methods: In this experimental study, after RNA extraction and cDNA syn- thesis from 50 non-obstructive azoospermic and 12 normal testis tissues, the expression ratios of genes were evaluated by real time polymerase chain reaction (PCR) technique. Hematoxcylin and eosin (H&E) staining was used for histological classification of testis tissues. For statistical analysis, one way analysis of variance (ANOVA) test was carried out.

Results: Our results showed a significant reduction in mRNA level of YBX2 in samples with impaired spermatogenesis (p<0.001) compared to samples with qualitatively normal spermatogenesis and normal spermatogenesis; however, in JHDM2A gene, despite sensible reduction in gene expression level in men with impaired spermatogenesis, no significant differences were shown (p>0.05). Furthermore in YBX2, a significant negative correlation was demonstrated between the efficiency score of spermatogenesis and the threshold cycle (CT) (r=-0.7, p<0.0001), whereas in JHDM2A, this negative correlation was not significant (r=-0.4, p=0.06).

Conclusion: Generally, these data indicated that YBX2 and JHDM2A genes may play an important role in male infertility, and suggested that these molecules can act as useful biomarkers for predicting male infertility.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393659PMC
http://dx.doi.org/10.22074/cellj.2015.518DOI Listing
April 2015

Evaluation of New ELISA based on rLsa63 - rLipL32 antigens for serodiagnosis of Human Leptospirosis.

Iran J Microbiol 2014 Jun;6(3):184-9

Department of Pathobiology, School of Public Health and Institute of Public Health Research, Tehran University of Medical Sciences, Tehran, Iran.

Background And Objectives: Timely diagnosis of leptospirosis is essential for an effective treatment. Large diversity of clinical symptoms has led leptospirosis diagnosis difficult. Researchers have conducted many tests with wide-range of sensitivity and specificity to achieve novel diagnostic procedures which have higher sensitivity and specificity compared with previous tests and which are more reliable and available to public laboratories. This study aimed to introduce Lsa63 and LipL32 proteins-based ELISA tests with more sensitivity, specificity, accuracy and convenience for public laboratories.

Materials And Methods: Recombinant forms of Lsa63 and LipL32 proteins were first generated. After coating these proteins, IgM and IgG ELISA tests were performed. 220 patients with suspicion of leptospirosis infection were selected for serum collection. The sera tests were carried out using MAT, IgM and IgG ELISA tests. In order to assess the performance of ELISA, the results of this test were compared with MAT.

Results: 30% of serum samples (n=65) in MAT were positive for leptospirosis infection, while ELISA tests including rLipL32- rLsa63-IgM and rLipL32-rLsa63-IgG showed 40.45% (n=89) and 38.63% (n=80) positive reaction, respectively.

Conclusion: Our results demonstrated that new ELISA tests based on mixing LipL32 and Lsa63 proteins, a novel mixture of recombinant antigens, are valuable to detect specific antibodies against pathogenic Leptospira in human serum and could be considered as helpful techniques in leptospirosis diagnosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393495PMC
June 2014

Development and evaluation of a Quadruplex Taq Man real-time PCR assay for simultaneous detection of clinical isolates of Enterococcus faecalis, Enterococcus faecium and their vanA and vanB genotypes.

Iran J Microbiol 2014 Oct;6(5):335-40

Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran.

Background And Objectives: We developed and evaluated the utility of a quadruplex Taqman real-time PCR assay that allows simultaneous identification of vancomycin-resistant genotypes and clinically relevant enterococci.

Materials And Methods: The specificity of the assay was tested using reference strains of vancomycin-resistant and susceptible enterococci. In total, 193 clinical isolates were identified and subsequently genotyped using a Quadruplex Taqman real-time PCR assay and melting curve analysis. Representative Quadruplex Taqman real-time PCR amplification curve were obtained for Enterococcus faecium, Enterococcus faecalis, vanA-containing E. faecium, vanB-containing E. faecalis.

Results: Phenotypic and genotypic analysis of the isolates gave same results for 82 enterococcal isolates, while in 5 isolates, they were inconsistent. We had three mixed strains, which were detected by the TaqMan real-time PCR assay and could not be identified correctly using phenotypic methods.

Conclusion: Vancomycin resistant enterococci (VRE) genotyping and identification of clinically relevant enterococci were rapidly and correctly performed using TaqMan real-time multiplex real-time PCR assay.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385574PMC
October 2014

The 763C>G Polymorphism of The Secretory PLA2IIa Gene Is Associated with Endometriosis in Iranian Women.

Int J Fertil Steril 2015 Jan-Mar;8(4):437-44. Epub 2015 Feb 7.

Department of Clinical Biochemistry and Medical Genetics, Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran.

Background: Endometriosis is a chronic gynecological disease resulting from complex interactions between genetic, hormonal, environmental and oxidative stress and intrinsic inflammatory components. The aim of this study was to investigate the potential association of the 763C>G polymorphism in the secretory phospholipase A2 group IIa gene (PLA2G2A) with the risk of endometriosis in Iranian women.

Materials And Methods: Ninety seven patients with endometriosis along with 107 women who were negative for endometriosis after laparoscopy and laparatomy, and served as the control group, were enrolled for this cross-sectional study. Samples were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method.

Results: Multivariate analysis was used to examine the association between the risk of endometriosis and the 763C>G polymorphism of PLA2G2A. Genotype distributions of PLA2G2A were significantly different between patients and the controls (p<0.001, OR=0.22, 95% CI=0.21-0.39). Correlation analysis showed that there was a significant association between the normal homozygous genotype and susceptibility to endometriosis (p<0.001).

Conclusion: The present study suggests that the 763C>G polymorphism of PLA2G2A plays an important role as an independent factor in the risk of endometriosis in Iranian women.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355930PMC
http://dx.doi.org/10.22074/ijfs.2015.4184DOI Listing
March 2015

Association between upstream purine complexes of human caveolin-1 gene and schizophrenia in qazvin province of iran.

Iran Red Crescent Med J 2014 Dec 30;16(12):e21484. Epub 2014 Nov 30.

Qazvin University of Medical Sciences, Qazvin, IR Iran.

Background: Caveolin is a multifunctional and scaffolding membrane protein, which involves cholesterol trafficking to plasma lipid microdomain. It organizes and targets synaptic parts of the neurotransmitter and neurotrophic receptor signaling pathways. Caveolins are encoded by CAV-1, 2 and 3 genes. Disruption of the CAV1 would likely ruin the neuronal signaling, which leads to symptoms of schizophrenia in predisposed individuals.

Objectives: The upper area of CAV-1 gene is highly conserved and can have a regulatory role in neurodegenerative diseases. This study was designed to find out the possible association of polymorphisms of this area and schizophrenia.

Patients And Methods: In a case-control study, 254 blood samples were obtained from 127 patients with schizophrenia and 127 well matched controls referred to 22 Bahman Hospital of Qazvin University of Medical Sciences (QUMS) in Qazvin province, Iran, using simple random sampling method. After extracting DNA, the upper region of the human CAV1- gene was amplified by PCR in all collected samples. The products were visualized by silver staining in 10% polyacrylamide gel and then sequenced.

Results: We detected nine homozygotes in patients and 15 in control subjects. Homozygosity was 7.08% and 11.8% in cases and control, respectively. Nine types homozygote haplotype were detected in upper region of the CAV1 gene in cases and controls. Three haplotypes were common in cases and controls; four haplotypes were seen in controls only and two in cases.

Conclusions: Our findings implied a significant correlation between some haplotypes of upper region of CAV1 gene and schizophrenia. Existence of some haplotypes and lack of another in CAV1 upstream can suggest a significant correlation between schizophrenia and some haplotypes.
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http://dx.doi.org/10.5812/ircmj.21484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341327PMC
December 2014

Effect of PPARδ agonist on stearoyl-CoA desaturase 1 in human pancreatic cancer cells: role of MEK/ERK1/2 pathway.

Can J Diabetes 2015 Apr 6;39(2):123-7. Epub 2015 Jan 6.

Cellular and Molecular Research Center, Faculty of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran. Electronic address:

Objective: The stearoyl-CoA desaturase 1 (SCD1), also known as Δ9-desaturase, is a regulatory enzyme in the cellular lipid modification process that has been linked to pancreatic cancer and diabetes. The aim of the present study was to investigate the effect of peroxisome proliferative-activated receptor δ (PPARδ) agonist and ERK1/2- and EGF receptor (EGFR)-dependent pathways on the expression of SCD1 in human pancreatic carcinoma cell line PANC-1.

Methods: PANC-1 cells cultured in RPMI-1640 were exposed to the commonly used MEK inhibitor PD98059, EGFR-selective inhibitor AG1478, and PPARδ agonist GW0742. Changes in mRNA, protein expression and activity index of SCD1 were then determined using real-time reverse transcription polymerase chain reaction, Western blot and gas liquid chromatography, respectively.

Results: The activity index and expression of SCD1 (p<0.01) decreased following treatment with PPARδ agonist at both mRNA and protein levels, whereas significant increases were observed after treatment with MEK or EGFR inhibitor. It was also found that the activity index of SCD1 were lower (p<0.01) in the combined treatment compared to the incubation with either inhibitor alone.

Conclusions: PPARδ and MEK/ERK1/2- and EGFR-dependent pathways affect the expression and activity of SCD1 in pancreatic cancer cells. Furthermore, the aforementioned kinase signalling pathways were involved in an inhibitory effect on the expression and activity of SCD1 in these cells, possibly via PPARδ activation.
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http://dx.doi.org/10.1016/j.jcjd.2014.09.006DOI Listing
April 2015