Publications by authors named "Kejin Zhang"

45 Publications

lncRNA MIR155HG Alleviates Depression-Like Behaviors in Mice by Regulating the miR-155/BDNF Axis.

Neurochem Res 2021 Apr 29;46(4):935-944. Epub 2021 Jan 29.

Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xian, 710069, China.

Depression is one of most common psychiatric disorders, and the detailed molecular mechanism remains to be fully elucidated. Brain-derived neurotrophic factor (BDNF) is a critical neurotrophic factor that is decreased and closely involved in the development of depression. Noncoding RNAs are central regulators of cellular activities that modulate target genes. However, the roles of long noncoding RNA (lncRNA) MIR155HG and miRNA-155 (miR-155) in the pathophysiology of depression are unclear. In the present study, we aimed to explore the effects of lncRNA MIR155HG and miR-155 on the development of depression and uncover the underlying molecular mechanism. Real-time quantitative polymerase chain reaction was used to examine the expression of MIR155HG and miR-155. Western blotting was applied to measure the expression of BDNF. A luciferase reporter assay was utilized to determine the regulatory relationship between MIR155HG and miR-155. Our current work found that lncRNA MIR155HG and BDNF levels decreased while miR-155 levels increased in the hippocampal region of CUMS (chronic unpredictable mild stress) mice, a well-accepted mouse model of depression. Moreover, MIR155HG rescued while miR-155 exacerbated the depression-like behaviors of CUMS mice. Through bioinformatics analysis and luciferase reporter assays, we found that MIR155HG directly bound to and negatively modulated the expression of miR-155. Moreover, increased miR-155 was found to repress the expression of BDNF, a critical neurotrophic factor that has been reported to alleviate the depression-like behaviors of CUMS mice. Our present study revealed that lncRNA MIR155HG protected CUMS mice by regulating the miR-155/BDNF axis. Our study aimed to understand the pathophysiology of depression and provided potential therapeutic targets to diagnose and treat depression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11064-021-03234-zDOI Listing
April 2021

Genetic Variants of the 9 Gene Are Associated with Nonspecific Intellectual Disability: A Family-Based Association Study.

Genet Test Mol Biomarkers 2020 Oct 29;24(10):625-631. Epub 2020 Sep 29.

School of Medicine, Northwest University, Xi'an, China.

Mutations within the myotubularin-related protein 9 gene (9) have been identified in several families with nonsyndromic intellectual disability (NSID), a generalized neurodevelopmental disorder; however, the relationship between 9 and NSID needs to be verified using a larger sample size. To explore whether genetic variants in the 9 gene are linked to susceptibility of NSID among the Chinese population. Seven single nucleotide polymorphisms (SNPs) of the 9 gene (rs4559208, rs3824211, rs2164272, rs2164273, rs1897951, rs6991606, and rs7815802) were analyzed using family-based association testing among 258 Han Chinese NSID families. Three SNPs of 9 were significantly associated with NSID ( = 2.152,  = 0.031 for rs4559208;  = 2.403,  = 0.016 for rs2164273; and  = 2.758,  = 0.006 for rs7815802). Three alleles of these SNPs were more likely to be transferred from the carrier parents to the affected offspring. Haplotypes constructed using these SNPs also showed a similar transmitting trend ( = 2.505,  = 0.012,  = 8.835, and global  = 0.032). Carriers with the G-G-C haplotype showed a higher risk of NSID (odds ratio = 1.46, 95% confidence interval [1.01-2.09],  = 0.04) than others. functional predictions supported an etiological role for these three SNPs in NSID biology. This study provides additional insights into the association of NSID with specific alleles, and haplotypes within the 9 gene. Genotypic analyses of the 9 gene should be considered for patients presenting with NSID of unknown etiology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/gtmb.2020.0145DOI Listing
October 2020

Revisiting the relationships of 2D:4D with androgen receptor (AR) gene and current testosterone levels: Replication study and meta-analyses.

J Neurosci Res 2020 02 29;98(2):353-370. Epub 2019 Jul 29.

Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an, China.

The relationships of digit ratio (2D:4D) with the length of AR (CAG)n, and testosterone levels from saliva and blood have been extensively debated over the years. This research including three studies further clarifies such controversies. To do so, we re-examined the relationships between the length of AR (CAG)n, 2D:4D, and current testosterone levels, through replication study and meta-analysis for each study. The results indicate: (a) the length of AR (CAG)n is not significantly associated with 2D:4D; (b) current testosterone levels are not significantly associated with the ratio; and (c) the length is not significantly associated with testosterone levels. Thus, AR (CAG)n and current testosterone levels are not significantly related to 2D:4D at individual level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jnr.24502DOI Listing
February 2020

Prediction of Alzheimer's disease with serum lipid levels in Asian individuals: a meta-analysis.

Biomarkers 2019 Jun 13;24(4):341-351. Epub 2019 Feb 13.

a College of Life Science, Institute of Health & Population Northwest University , Xi'an , China.

The serum lipid profile has become a routine clinical test and used as an important predictor for Alzheimer's disease (AD), although its predictive value remains undetermined. To evaluate the role of serum lipid levels in predicting the risk of AD. Meta-analyses were conducted using Comprehensive Meta-analyses (CMA) software to investigate the association between four conventional serum lipid profile parameters and the risk of AD, focused on samples from Asian. In total, 3423 AD patients and 6127 healthy participants were involved. The results demonstrated that AD patients showed higher LDL-C and TC levels (SMD = 0.27, 95% CI: 0.04-0.51,  = 0.02 for LDL-C; SMD = 0.25, 95% CI: 0.05-0.46,  = 0.02 for TC) compared with those of healthy controls. People with higher LDL-C and/or TC levels had an increased risk of AD (OR = 1.64, 95% CI: 1.07-2.51 for LDL-C and OR = 1.58, 95% CI: 1.10-2.92 for TC). This study provided evidence that serum LDL-C and TC levels were associated with the risk of AD in Asian individuals. The routine lipid profile may be useful for AD diagnosis, monitoring and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/1354750X.2019.1571633DOI Listing
June 2019

Mutations of ARX and non-syndromic intellectual disability in Chinese population.

Genes Genomics 2019 01 25;41(1):125-131. Epub 2018 Sep 25.

Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), Institute of Population and Health, Northwest University, Xi'an, 710069, China.

Mutations of Aristaless-related homeobox (ARX) gene were looked as the third cause of non-syndromic intellectual disability (NSID), while the boundary between true disease-causing mutations and non-disease-causing variants within this gene remains elusive. To investigate the relationship between ARX mutations and NSID, a panel comprising six reported causal mutations of the ARX was detected in 369 sporadic NSID patients and 550 random participants in Chinese. Two mutations, c.428_451 dup and p.G286S, may be disease-causing mutations for NSID, while p.Q163R and p.P353L showed a great predictive value in female NSID diagnosis with significant associations (X = 19.60, p = 9.54e-6 for p.Q163R; X = 25.70, p = 4.00e-07 for p.P353L), carriers of these mutations had an increased risk of NSID of more than fourfold. Detection of this panel also predicted significant associations between genetic variants of the ARX gene and NSID (p = 3.73e-4). The present study emphasized the higher genetic burden of the ARX gene on NSID in the Chinese population, molecular analysis of this gene should be considered for patients presenting NSID of unknown etiology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13258-018-0745-6DOI Listing
January 2019

Genetic variants of SLC12A3 modulate serum lipid profiles in a group of Mongolian pedigree population.

Lipids Health Dis 2018 Apr 16;17(1):83. Epub 2018 Apr 16.

Clinical Research Center of the Affiliated Hospital, Inner Mongolia Medical University, Hohhot, 010050, Inner Mongolia, China.

Background: The serum lipid profile, including LDL-C level, is associated with hypertension which is the major cause of cerebrovascular disease (CVD) amounting 30% of global death rate. Previous work also demonstrated important roles of genetic variants of SLC12A3 gene on human CVD, hypertension and other diseases in Mongolian population. However, the relationship between SLC12A3 gene polymorphisms on individuals' lipid profile is still unknown.

Methods: A panel of 15 SNPs of SLC12A3 gene was genotyped within a 424 Mongolians pedigree cohort. The associations between SLC12A3 polymorphisms and four lipid profiles were analyzed by family-based association test (FBAT) and confirmed with haplotype analysis.

Results: From both single site and haplotype analyses, the results demonstrated a close relationship between SLC12A3 polymorphisms and LDL-C level. Two SNPs, rs5803 and rs711746 showed significant associations with individuals' serum LDL-C level (z = - 2.08, P  = 0.038; z = 2.09, P  = 0.023, respectively), and distribution of haplotypes constructed by two SNPs also associated with participants' serum LDL-C level, significantly (Global Chi = 9.06 df = 3, P = 0.028).

Conclusion: Our results demonstrated the importance of SLC12A3 polymorphisms in individuals' difference about their serum lipid profiles, thereby providing evidence that the genetic variants may contribute to CVD development via modulating person's LDL-C level and blood pressure, in certain contexts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12944-018-0737-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902855PMC
April 2018

MiR-767 promoted cell proliferation in human melanoma by suppressing CYLD expression.

Gene 2018 Jan 18;641:272-278. Epub 2017 Oct 18.

Department of Dermatology, Liaocheng City People's Hospital, Liaocheng City, Shandong Province 252000, People's Republic of China. Electronic address:

MicroRNAs (miRNAs) have emerged as critical regulators for cancer development and progression of human melanoma. However, the potential molecular mechanism of miR-767 in human melanoma has not been intensively investigated. In this present study, we confirmed that miR-767 was frequently up-regulated in human melanoma tissues and cell lines. Ectopic expression of miR-767 promoted cell proliferation in human melanoma cell lines A375 and WM35, whereas miR-767-in reversed the function. Bioinformatics analysis revealed that cylindromatosis (CYLD) was hypothesized to be a possible target gene of miR-767, and this was confirmed by luciferase activity assay. Knockdown of CYLD counteracted the proliferation arrest by miR-767-in in melanoma cells A375 and WM35. In conclusion, our study indicated that miR-767 acted as a role of tumor promoter by targeting CYLD in human melanoma, and might serve as a prognostic or therapeutic target for human melanoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gene.2017.10.055DOI Listing
January 2018

Independent self-construal mediates the association between CYP19A1 gene variant and subjective well-being.

Conscious Cogn 2017 10 6;55:205-213. Epub 2017 Sep 6.

Shaanxi Key Laboratory for Animal Conservation, Northwest University, Xi'an 710069, China; Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Northwest University, Xi'an 710069, China; College of Life Science, Northwest University, Xi'an 710069, China; Institute of Population and Health, Northwest University, Xi'an 710069, China. Electronic address:

Testosterone and estrogen are involved in self-related behavioral dispositions and experiences of subjective well-being. In this study, we investigated to what extent the aromatase (CYP19A1) gene, which encodes an enzyme in converting testosterone into estrogen, contributes to subjective well-being and in another self-related disposition: independent and interdependent self-construal. In study 1, a meta-analysis showed that the GG genotype of CYP19A1 (a G/A substitution at Val80, rs700518) was associated with higher testosterone and lower estradiol. In study 2, an empirical study of individuals with the GG (n=115), AG (n=286) and AA (n=193) genotypes indicated that individuals with the GG genotype exhibited higher independent self-construal and higher subjective well-being. The association between the GG genotype of CYP19A1 Val80 and subjective well-being was mediated by the independent self-construal. Our findings reinforce the idea that personality traits such as independent self-construal explain the link between genetic variant and subjective well-being.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.concog.2017.08.012DOI Listing
October 2017

Revisiting the impact of OXTR rs53576 on empathy: A population-based study and a meta-analysis.

Psychoneuroendocrinology 2017 Jun 9;80:131-136. Epub 2017 Mar 9.

Center for Brain and Cognitive Sciences and School of Psychological and Cognitive Sciences, Peking University, Beijing 100871, China; Beijing Key Laboratory of Behavior and Mental Health, Peking University, Beijing 100871, China; PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China. Electronic address:

Oxytocin in the brain is related to empathy, which refers to the ability to understand and share others' internal states or responses. Previous studies have investigated the impact of OXTR rs53576, the most intensively examined polymorphism in the oxytocin receptor (OXTR) gene, on individual differences in empathy. However, these studies produced inconsistent results. In the current study, we reexamined the association of OXTR rs53576 with empathy in a relatively large population (N=1830) and also evaluated the association by a comprehensive meta-analysis (N=6631, 13 independent samples). The replication study indicated that OXTR rs53576 was indeed associated with individual differences in empathy. Individuals with a greater number of G alleles showed better empathic ability, particularly in fantasizing other's feelings and actions. The meta-analysis not only confirmed this association, but also indicated that the impact of this polymorphism was significant in both Europeans and Asians. These findings provide convincing evidence for the impact of OXTR rs53576 on empathy, highlighting the importance of OXTR gene in individuals' social cognition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psyneuen.2017.03.005DOI Listing
June 2017

SLC12A3 variants modulate LDL cholesterol levels in the Mongolian population.

Lipids Health Dis 2017 Feb 6;16(1):29. Epub 2017 Feb 6.

Clinical Research Center of the Affiliated Hospital, Inner Mongolia Medical University, Hohhot, 010050, Inner Mongolia, China.

Background: Abnormalities in lipid metabolism are crucial factors in the pathogenesis of cardiovascular disease (CVD). Variants of many genes have been verified to confer risk for lipid metabolism abnormalities. However, the relationship between genetic variants of the NCC-encoding SLC12A3 gene and lipid metabolism in the Mongolian population remains unclear. In the present study, we aimed to elucidate the effects of SLC12A3 variants on Mongolian lipid metabolism, including total cholesterol (TCHO), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c).

Methods: A randomly selected population of Mongolians (n = 331) from China underwent clinical testing. An ANOVA test, Kruskal-Wallis H test (K-W test) and haplotype analysis were used to evaluate the association between the levels of lipids (TCHO, TG, LDL-c, and HDL-c) and polymorphisms in SLC12A3 loci.

Results: We identified three single nucleotide polymorphisms (SNPs) rs5803, rs2010501 and rs711746 in the SLC12A3 gene that were significantly associated with an individual's serum LDL-c level. Haplotypes combining these SNPs also showed the same trend (all p values < 0.01). Furthermore, the influence of SLC12A3 genetic polymorphisms on differences in individual serum LDL-c levels remained significant, even after we controlled gender, and demographic and other non-genetic factors.

Conclusion: These results suggest that variants of the SLC12A3 gene confer susceptibility to the abnormal serum LDL-c level in the Mongolian population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12944-017-0413-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294767PMC
February 2017

The c.553G>T Genetic Variant of the APOA5 Gene and Altered Triglyceride Levels in the Asian Population: A Meta-Analysis of Case-Control Studies.

Genet Test Mol Biomarkers 2016 Dec 4;20(12):758-765. Epub 2016 Nov 4.

College of Life Science, Institute of Preventive Genomic Medicine, Northwest University , Xi'an, China .

Aim: To explore the association of the APOA5 gene c.553G>T polymorphism with hypertriglyceridemia (HTG) susceptibility and altered triglyceride levels.

Methods: We searched the PubMed, Google Scholar, and CNKI databases for published studies relating to analyses of these associations. Case-control and comparative studies of the association between the APOA5 c.553G>T variant and altered triglyceride levels were included. In total, the meta-analysis involved 10 studies on HTG, which provided 2219 cases and 3401 controls. To measure the correlation between the c.553G>T polymorphism and HTG susceptibility, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The overall OR was calculated using a random-effects model.

Results: Compared with APOA5 c.553 GG carriers, c.553T carriers displayed an increased risk of HTG in the Asian population, with an overall random effects OR of 3.55 (95% CI: 2.46-5.13) in the dominant model. There was significant heterogeneity among the studies (P: Chi = 45.80, I = 75.98%), which may be largely explained by certain patient types. Both the sensitivity analysis and publication bias suggested that the overall result was acceptable. Subgroup analysis showed a large difference in serum triglyceride levels based on the c.553 G > T polymorphism in healthy individuals and HTG patients. APOA5 c.553T carriers exhibit higher triglyceride levels than GG carriers.

Conclusion: Our results suggest that APOA5 c. 553T is an independent risk factor for HTG and increased triglyceride levels in the Asian population. APOA5 c. 553T could be employed as a genetic risk marker for HTG and increased triglyceride levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/gtmb.2016.0047DOI Listing
December 2016

Pustular rheumatoid neutrophilic dermatitis with Koebner phenomenon.

Indian J Dermatol Venereol Leprol 2016 Sep-Oct;82(5):569-71

Department of Dermatology, Shandong Provincial Hospital for Skin Diseases, Shandong University; Department of Dermatology, Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, Shandong, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/0378-6323.183637DOI Listing
April 2017

Genetic Polymorphism of GABRR2 Modulates Individuals' General Cognitive Ability in Healthy Chinese Han People.

Cell Mol Neurobiol 2017 Jan 27;37(1):93-100. Epub 2016 Feb 27.

Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), Institute of Population and Health, College of Life Science, Northwest University, Xi'an, 710069, China.

Previous studies have indicated that the cognitive impairment or deficit is associated with GABAergic signaling in central nervous system. Inspired by the finding that receptor GABRR2 modulates concentration of GABA and phasic inhibitory GABAergic transmission in brain. This study investigated to what extent a genetic variant (c.1423C>T, rs282129) of GABRR2 gene modulates individuals' general cognitive ability in 987 Chinese Han people. Results showed a significant influence of GABRR2 gene polymorphism on individuals' Raven's Standard Progressive Matrices (RSPM) performance (F = 3.58, P = .028 by ANOVA and χ  = 9.35, P = .009 by K-W test, respectively), even if non-genetic factors were partialed out (gender, major, types of birthplace, and socioeconomic index) (B = -.67, SE = .26, t = 2.63, P = .009). The finding provided a strong evidence, to our knowledge, for the view that genetic variant of GABRR2 gene may contribute to the difference of individuals' general cognitive ability, independently.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10571-016-0347-2DOI Listing
January 2017

Polymorphic variation in CHAT gene modulates general cognitive ability: An association study with random student cohort.

Neurosci Lett 2016 Mar 6;617:122-6. Epub 2016 Feb 6.

Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), Institute of Population and Health, College of Life Science, Northwest University, Xi'an 710069, China. Electronic address:

The choline O-acetyltransferase (CHAT) gene has been associated with various human disorders that involve cognitive impairment or deficiency. However, the influence of disease-associated variants of CHAT on normal individuals remains dubious. Here we demonstrated the impact of CHAT sequence variants (G-120A) on general human cognitive ability in a cohort of 750 Chinese undergraduate students. A multiple choice questionnaire was used to obtain basic demographic information, such as parents' occupations and education levels. We also administered and scored the Raven's Standard Progressive Matrices (RSPM). A one-way analysis of variance (ANOVA) and Kruskal-Wallis test (K-W) revealed a significant association between sequence polymorphisms of G-120A and individuals' Raven score (p=0.031 for ANOVA and p=0.026 for K-W tests). Moreover, further hierarchical analysis showed a similar trend in the association between G-120A variants and Raven scores only in the female subjects (p=0.008 for ANOVA and p=0.024 for K-W tests) but not in the male subjects. The results of a multiple linear regression confirmed that after we controlled gender, age, birthplace and other non-genetic factors, CHAT G-120A polymorphisms still significantly influenced individual Raven scores (B=-0.70, SE=0.28, t=-2.50, p=0.013). Our results demonstrated that sequence variants of CHAT were associated with human cognitive ability in not only patients with psychiatric disorders but also normal healthy individuals. However, some issues remained indeterminable, such as gender differences and the extent of the influence on individuals' general cognitive abilities; thus, the further research using an independent random sample was required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neulet.2016.02.002DOI Listing
March 2016

Polymorphisms in the SLC12A3 Gene Encoding Sodium-Chloride Cotransporter are Associated with Hypertension: A Family-Based Study in the Mongolian Population.

Kidney Blood Press Res 2016 8;41(1):18-28. Epub 2016 Jan 8.

Clinical Research Center of the Affiliated Hospital, Inner Mongolia Medical University, Hohhot, China.

Background/aims: Hypertension or persistent high blood pressure (BP) is a leading cause of death worldwide. Extensive evidence indicates that the thiazide-sensitive Na+-Cl- cotransporter (NCC) affects BP via regulation of renal sodium reabsorption. However, the relationship between genetic variants of the NCC-encoding SLC12A3 gene and hypertension in the Mongolian population is still ambiguous. In this study, we aimed to genotype an extended cohort of hypertensive Mongolian families for polymorphisms in the SLC12A3 locus.

Methods: Eighty-eight families with a history of hypertension, including parents, offspring, and relatives underwent clinical testing. Family-based association tests and haplotype analysis were used to evaluate the association between hypertension and polymorphisms in the SLC12A3 locus.

Results: We identified three single nucleotide polymorphisms (SNPs), one in the SLC12A3 coding region (p = 0.05) and two in the intron (p = 0.02 and p = 0.07), which were significantly associated with the hypertension phenotype. Haplotype-specific association tests confirmed the correlation of these SNPs with hypertension (p < 0.05).

Conclusion: These results suggest that SNPs in the SLC12A3 gene confer susceptibility to hypertension in the Mongolian population. Further research is needed to validate the functional role of SLC12A3 polymorphisms in hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000368543DOI Listing
December 2016

A New Role for LOC101928437 in Non-Syndromic Intellectual Disability: Findings from a Family-Based Association Test.

PLoS One 2015 19;10(8):e0135669. Epub 2015 Aug 19.

Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), College of Life Science, Institute of Population and Health, Northwest University, Xi'an, China.

Non-syndromic intellectual disability (NSID) is mental retardation in persons of normal physical appearance who have no recognisable features apart from obvious deficits in intellectual functioning and adaptive ability; however, its genetic etiology of most patients has remained unknown. The main purpose of this study was to fine map and identify specific causal gene(s) by genotyping a NSID family cohort using a panel of markers encompassing a target region reported in a previous work. A total of 139 families including probands, parents and relatives were included in the household survey, clinical examinations and intelligence tests, recruited from the Qinba mountain region of Shannxi province, western China. A collection of 34 tagged single nucleotide polymorphisms (tSNPs) spanning five microsatellite marker (STR) loci were genotyped using an iPLEX Gold assay. The association between tSNPs and patients was analyzed by family-based association testing (FBAT) and haplotype analysis (HBAT). Four markers (rs5974392, rs12164331, rs5929554 and rs3116911) in a block that showed strong linkage disequilibrium within the first three introns of the LOC101928437 locus were found to be significantly associated with NSID (all P<0.01) by the FBAT method for a single marker in additive, dominant and recessive models. The results of haplotype tests of this block also revealed a significant association with NSID (all P<0.05) using 2-window and larger HBAT analyses. These results suggest that LOC101928437 is a novel candidate gene for NSID in Han Chinese individuals of the Qinba region of China. Although the biological function of the gene has not been well studied, knowledge about this gene will provide insights that will increase our understanding of NSID development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0135669PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545728PMC
May 2016

Racial disparity in breast cancer survival: the impact of pre-treatment hematologic variables.

Cancer Causes Control 2015 Jan 31;26(1):45-56. Epub 2014 Oct 31.

Division of Population Science, Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA.

Purpose: A survival disparity of black versus white breast cancer patients has been extensively documented but not adequately explained. Blacks and whites also have significant differences in hematologic traits including hemoglobin (HGB). However, a link between survival disparity and hematologic differences has not been reported. We aimed to explore the effect of pre-treatment hematologic variables on this survival disparity.

Methods: We sequentially matched 443 black patients, using a minimum distance approach, to four different sets of 443 whites on demographics (age, year of diagnosis, smoking, and drinking status), tumor presentation (all demographic variables plus tumor stage, grade, and hormone receptor status), treatment (all presentation variables plus surgery, chemotherapy, radiation therapy, and hormone therapy), and presentation plus pre-treatment hematologic variables. Racial survival for each matched dataset was analyzed by Cox proportional hazards model.

Results: We found that white patients matched on demographic characteristics had more favorable survival than blacks [hazard ratio (HR) 0.57, 95 % confidence interval (CI) 0.42-0.77, p log-rank = 0.0002]. Presentation match diminished this disparity [HR 0.72 (0.54-0.95), p log-rank = 0.0199], which was not further reduced in treatment match [HR 0.73 (0.55-0.96), p log-rank = 0.0249]. However, the survival disparity was largely reduced when pre-treatment level of HGB or red blood cell distribution width was further matched in addition to presentation match [HR 0.83 (0.64-1.09), p log-rank = 0.1819 and HR 0.83 (0.64-1.09), p log-rank = 0.1760, respectively].

Conclusions: We found that in our patient population, differences in tumor presentation and certain pre-treatment hematologic traits, but not treatment, were associated with the survival disparity between black and white breast cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10552-014-0481-4DOI Listing
January 2015

Aspartate aminotransferase to platelet ratio index as a prospective predictor of hepatocellular carcinoma risk in patients with chronic hepatitis B virus infection.

J Gastroenterol Hepatol 2015 Jan;30(1):131-138

Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.

Background And Aim: APRI (aspartate aminotransferase [AST] to platelet ratio index) is widely used to assess fibrosis and cirrhosis risk, especially in hepatitis C virus (HCV)-infected patients. Few studies have evaluated APRI and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) risk. Prospective evidence is needed to assess whether APRI predicts HCC risk in HBV patients.

Method: In a prospectively enrolled clinical cohort of 855 HBV patients with a 1-year exclusion window (followed for > 1 year and did not develop HCC within 1 year), the predictive value of APRI in HCC risk was evaluated by Cox proportional hazards model using univariate and multivariate analyses and longitudinal analysis.

Results: Higher APRI prospectively conferred a significantly increased risk of HCC in univariate analysis (quartile analysis, P trend = 2.9 × 10(-7) ). This effect remained highly significant after adjusting for common host characteristics but not cirrhosis (P trend = 7.1 × 10(-5) ), and attenuated when cirrhosis is adjusted (P trend = 0.021). The effect remained prominent when the analysis was restricted to patients with a more stringent 2-year exclusion window (P trend = 0.008 in quartile analysis adjusting all characteristics including cirrhosis), indicating that the association was unlikely due to including undetected HCC patients in the cohort, thus minimizing the reverse-causation limitation in most retrospective studies. Longitudinal comparison demonstrated a persistently higher APRI value in HBV patients who developed HCC during follow-up than those remaining cancer free.

Conclusion: APRI might be a marker of HCC risk in HBV patients in cirrhosis-dependent and -independent manners. Further studies are warranted to validate this finding and test its clinical applicability in HCC prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgh.12664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418451PMC
January 2015

Modeling the overall survival of patients with advanced-stage non-small cell lung cancer using data of routine laboratory tests.

Int J Cancer 2015 Jan 5;136(2):382-91. Epub 2014 Jun 5.

Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA; College of Life Sciences, Northwest University, Xi'an, China.

Cancer patients undergo routine clinical monitoring with an array of blood tests that may carry long-term prognostic information. We aimed to develop a new prognostic model predicting survival for patients with advanced non-small cell lung cancer (NSCLC), based on laboratory tests commonly performed in clinical practice. A cohort of 1,161 stage IIIB or IV NSCLC patients was divided into training (n = 773) and testing (n = 388) cohorts. We analyzed the associations of 32 commonly tested laboratory variables with patient survival in the training cohort. We developed a model based on those significant laboratory variables, together with important clinical variables. The model was then evaluated in the testing cohort. Five variables, including albumin, total protein, alkaline phosphatase, blood urea nitrogen and international normalized ratio, were significantly associated with patient survival after stepwise selection. A model incorporating these variables classified patients into low-, medium- and high-risk groups with median survival of 16.9, 7.2 and 2.1 months, respectively (p < 0.0001). Compared with low-risk group, patients in the medium- and high-risk groups had a significantly higher risk of death at 1 year, with hazard ratio (HR) of 1.95 (95% CI 1.62-2.36) and 5.22 (4.30-6.34), respectively. These results were validated in the testing cohort. Overall, we developed a prognostic model relying entirely on readily available variables, with similar predictive power to those which depend on more specialized and expensive molecular assays. Further study is necessary to validate and further refine this model, and compare its performance to models based on more specialized and expensive testing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.28995DOI Listing
January 2015

Genetic variations in colorectal cancer risk and clinical outcome.

World J Gastroenterol 2014 Apr;20(15):4167-77

Kejin Zhang, Sushmita Mukherjee, Fenil Patel, Hushan Yang, Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, United States.

Colorectal cancer (CRC) has an apparent hereditary component, as evidenced by the well-characterized genetic syndromes and family history associated with the increased risk of this disease. However, in a large fraction of CRC cases, no known genetic syndrome or family history can be identified, suggesting the presence of "missing heritability" in CRC etiology. The genome-wide association study (GWAS) platform has led to the identification of multiple replicable common genetic variants associated with CRC risk. These newly discovered genetic variations might account for a portion of the missing heritability. Here, we summarize the recent GWASs related to newly identified genetic variants associated with CRC risk and clinical outcome. The findings from these studies suggest that there is a lack of understanding of the mechanism of many single nucleotide polymorphisms (SNPs) that are associated with CRC. In addition, the utility of SNPs as prognostic markers of CRC in clinical settings remains to be further assessed. Finally, the currently validated SNPs explain only a small fraction of total heritability in complex-trait diseases like CRC. Thus, the "missing heritability" still needs to be explored further. Future epidemiological and functional investigations of these variants will add to our understanding of CRC pathogenesis, and may ultimately lead to individualized strategies for prevention and treatment of CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3748/wjg.v20.i15.4167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3989953PMC
April 2014

Preoperative platelet count associates with survival and distant metastasis in surgically resected colorectal cancer patients.

J Gastrointest Cancer 2013 Sep;44(3):293-304

Division of Population Science, Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.

Objective: Platelets have been implicated in cancer metastasis and prognosis. No population-based study has been reported as to whether preoperative platelet count directly predicts metastatic recurrence of colorectal cancer (CRC) patients.

Design: Using a well-characterized cohort of 1,513 surgically resected CRC patients, we assessed the predictive roles of preoperative platelet count in overall survival, overall recurrence, as well as locoregional and distant metastatic recurrences.

Results: Patients with clinically high platelet count (≥400 × 10(9)/L) measured within 1 month before surgery had a significantly unfavorable survival (hazard ratio [HR] = 1.66, 95 % confidence interval [CI] 1.34-2.05, P = 2.6 × 10(-6), P(log rank) = 1.1 × 10(-11)) and recurrence (HR = 1.90, 1.24-2.93, P = 0.003, P(log rank) = 0.003). The association of platelet count with recurrence was evident only in patients with metastatic (HR = 2.81, 1.67-4.74, P = 1.1 × 10(-4), P(log rank) = 2.6 × 10(-6)) but not locoregional recurrence (HR = 0.59, 95 % CI 0.21-1.68, P = 0.325, P(log rank) = 0.152). The findings were internally validated through bootstrap resampling (P < 0.01 at 98.6 % of resampling). Consistently, platelet count was significantly higher in deceased than living patients (P < 0.0001) and in patients with metastatic recurrence than locoregional (P = 0.004) or nonrecurrent patients (P < 0.0001). Time-dependent modeling indicated that the increased risks for death and metastasis associated with elevated preoperative platelet counts persisted up to 5 years after surgery.

Conclusion: Our data demonstrated that clinically high level of preoperative platelets was an independent predictor of CRC survival and metastasis. As an important component of the routinely tested complete blood count panel, platelet count may be a cost-effective and noninvasive marker for CRC prognosis and a potential intervention target to prevent metastatic recurrence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12029-013-9491-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3748145PMC
September 2013

A family-based association study of dopamine receptor D4 and mental retardation in Qinba region of China.

Neurosci Lett 2012 May 15;516(1):1-4. Epub 2012 Feb 15.

Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), College of Life Science, Institute of Population and Health, Northwest University, Xi'an 710069, China.

Dopamine receptor D4 (DRD4) is activated by the neurotransmitter dopamine and links to many neurological and psychiatric conditions because of its close relationship with prefrontal cortex and other important brain regions. To explore the possibility that genetic variants of DRD4 gene predispose to children with mental retardation (MR), five target SNPs of DRD4 were selected and genotyped in the samples of 163 MR pedigrees from the Qinba region of China. Two SNPs (rs752306 and rs3758653) showed weak association with MR (the P values were 0.022 and 0.015 for dominant model, and 0.027 and 0.015 for recessive model, respectively). Although they did not bear the multiple testing corrections, the haplotype which contained rs3758653 exhibited a significant association with MR (global P values were 0.018 for dominant model and 0.028 for recessive model, respectively). The in silico analysis also indicated that rs752306 and rs3758653 would be biologically meaningful SNPs. Therefore, the present study suggested that the genetic variants of DRD4 gene may play an important role in human MR. Further investigations, such as confirmation with other independent samples and functional studies, may elucidate their effect on gene expression and MR susceptibility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neulet.2012.02.017DOI Listing
May 2012

An association study on the polymorphisms of dopaminergic genes with working memory in a healthy Chinese Han population.

Cell Mol Neurobiol 2012 Aug 24;32(6):1011-9. Epub 2012 Feb 24.

Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), College of Life Science, Institute of Population and Health, Northwest University, Xi'an, China.

Working memory (WM) is a highly heritable cognitive trait that is involved in many higher-level cognitive functions. In the past few years, much evidence has indicated that the reduction of dopamine activity in human brain can impair the WM system of the neuropsychiatric disorders. In this study, we hypothesized that some genes in the dopamine system were involved in the individual difference of the cognitive ability in healthy population. To confirm this hypothesis, a population-based study was performed to examine the effects of COMT, DAT (1), DRD (1), DRD (2), DRD (3), and DRD (4) on WM spans. Our results indicated there were significant associations of TaqIA and TaqIB in DRD (2) with digital WM span, respectively (χ(2) = 9.460, p = 0.009; χ(2) = 6.845, p = 0.033). On the other hand, we found a significant interaction between Ser9Gly in DRD (3) and TaqIA of DRD (2) on digital WM span (F = 3.207, p = 0.013). COMT, DAT (1) , DRD (1), and DRD (4), however, had no significant effects on digital and spatial WM spans (χ(2)<3.84, p > 0.05). These preliminary results further indicated that certain functional variants in dopamine system, such as TaqIA and TaqIB of DRD (2), were possibly involved in difference of WM in a healthy population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10571-012-9817-3DOI Listing
August 2012

A family-based association study of DIO2 and children mental retardation in the Qinba region of China.

J Hum Genet 2012 Jan 3;57(1):14-7. Epub 2011 Nov 3.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Institute of Population and Health, Northwest University, Xi'an, China.

Deiodinase enzyme II (DIO2) has an important role in individuals' thyroid hormones' level, the development of central and peripheral nervous systems and characterized by mental retardation (MR). The DIO2 gene was genotyped by using five haplotype-tagging single-nucleotide polymorphisms (SNPs) in 157 Chinese MR high-density family pedigrees, including 452 nuclear families and >1460 persons. The single marker and haplotype analyses were performed by Family-based Association Tests (FBAT). Three SNPs had P-values <0.05 in at least one inherited model survived with the correction. Several haplotypes composed of these SNPs were also associated with MR. The in silico analyses identified that one of the SNPs, rs1388378, may be a functional SNP. However, further in vitro studies of this SNP should be considered in elucidating its effect on gene expression and the possible role in MR susceptibility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/jhg.2011.121DOI Listing
January 2012

An association study of the genetic polymorphisms in 13 neural plasticity-related genes with semantic and episodic memories.

J Mol Neurosci 2012 Feb 5;46(2):352-61. Epub 2011 Jul 5.

Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), College of Life Science, Institute of Population and Health, Xi'an, 710069, China.

Semantic and episodic memories were two different attributes of long-term memory. In the past few years, plenty of physiological evidence has indicated that neural plasticity is involved in the formation of long-term memory. In the present study, we hypothesized that some functional variants of neural plasticity-related genes were related to episodic and semantic memories. To confirm this hypothesis, we examined the relationship of 13 plasticity-related genes with episodic and semantic memories. The results indicated that there was a statistically significant difference in semantic memory scores among the three genotype groups of T267C in 5-HT ( 6 ) (χ (2) = 16.638, p = 0.0002). However, the functional variations in BDNF, COMT, DBH, DRD ( 2 ), DRD ( 3 ), DRD ( 4 ), MAOA, TPH ( 2 ), 5-HT ( 2A ), GRM ( 1 ), and GRIN2B had no observable effects on the memories. Our preliminary results confirm the hypothesis that a small number of functional variants of the neural plasticity-related genes, such as T267C in 5-HT ( 6 ), play important roles in human specific memory.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12031-011-9592-5DOI Listing
February 2012

Variants in COMT and DBH influence on response inhibition ability in Chinese Han females.

Cell Mol Neurobiol 2011 Nov 19;31(8):1163-9. Epub 2011 Jun 19.

Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), College of Life Science, Institute of Population and Health, Northwest University, Xi'an 710069, China.

Catechol-O-methyltransferase (COMT) and dopamine-beta hydroxylase (DBH) are key enzymes to breakdown dopamine. Some previous studies have indicated that val158met in COMT and 19 bp insertion/deletion in 5' flank of DBH are related to the performance of executive function. To further investigate the associations of the two genes with executive function, we performed a population-based study in a Chinese Han population. The results indicated that val158met in COMT and the 19 bp insertion/deletion of DBH were associated with the average reaction time of response inhibition in female group (P = 0.01, P = 0.03), respectively. Furthermore, there was a significant interaction of the two genes on the reaction time (P = 0.006). This present study suggests that not only do COMT and DBH influence independently on response inhibition in females, but also exert a significant interaction on response inhibition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10571-011-9717-yDOI Listing
November 2011

Association analysis of TPH2, 5-HT2A, and 5-HT6 with executive function in a young Chinese Han population.

J Neurogenet 2011 Mar 4;25(1-2):27-34. Epub 2011 Apr 4.

Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), College of Life Science, Institute of Population and Health, Xi'an, China.

The 5-hydroxytryptamine (5-HT) system is widely distributed in the central nervous system. A growing body of evidence has suggested that the neurotransmitter system is implicated in the functions of the prefrontal cortex. So far, several studies have revealed that some functional genetic variants in TPH2, 5-HT2A, and 5-HT6 genes are possibly related to executive function. To investigate the potential influences of TPH2, 5-HT2A, and 5-HT6 on the components of executive function, the authors performed a population-based study with standard cognitive paradigms in a young Chinese Han group. The results indicated that -703 G/T polymorphism of TPH2 was associated with the performance of response inhibition (p = .002) and the T allele carriers (TT and GT) had fewer errors than the noncarriers (GG) did in the response inhibition test. Furthermore, there were no significant associations of the T102C in 5-HT2A and T267C in 5-HT6 with the components of executive function after correcting for multiple tests (p > .05). The present study suggests that TPH2 contributes distinctively to the inhibition domain of executive function, whereas 5-HT2A and 5-HT6 show no striking effects on executive function in the Chinese Han population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/01677063.2011.569804DOI Listing
March 2011

Polymorphisms in the DLG3 gene is not associated with non-syndromic mental retardation in the Chinese Han population of Qin-Ba mountain.

Cell Mol Neurobiol 2011 Jul 3;31(5):695-700. Epub 2011 Mar 3.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Institute of Population and Health, College of Life Science, Northwest University, People's Republic of China.

Discs-large-related 3 (DLG3), a member of the membrane-associated guanylate kinases (MAGUKs) protein family, playing an important role in regulating NMDA signal pathway and contributing to synaptic plasticity, may have an influence on the susceptibility of non-syndromic mental retardation (NSMR). To investigate the possible genetic contribution of DLG3 gene to the NSMR of Chinese Han population, we performed an association study of 556 subjects (118 NSMR, 116 borderline NSMR, and 322 controls in 275 males and 281 females) from Qin-Ba mountain region of Shaanxi province in the northwest of China by five common SNPs in the gene. The results showed that there was no positive association between the genetic variations of DLG3 and NSMR. In conclusion, the results of this study indicated that DLG3 did not associate with NSMR in Chinese Han population; however, further studies are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10571-011-9666-5DOI Listing
July 2011

Variations in 5-HT2A influence spatial cognitive abilities and working memory.

Can J Neurol Sci 2011 Mar;38(2):303-8

Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Institute of Population and Health Henan University of Science and Technology, Luoyang, China.

Background: 5-hydroxytryptamine receptor 2A (5-HT2A) participates in diverse psychiatric disorders by regulating the activity of serotonin. Some previous studies have also suggested that the receptor is involved in cognitive abilities of disease groups. We hypothesize that some functional genetic variants in 5-HT2A have certain specific influences on cognitive abilities in a normal population.

Method: To confirm this hypothesis, two polymorphisms (rs6313 and rs4941573) in 5-HT2A were selected, and a population-based study was performed in a young healthy Chinese Han cohort.

Results: The results indicated that the rs6313 and rs4941573 were associated with touching blocks and mental rotation-3D error ratio in males, and the rs4941573 was associated with visuo-spatial working memory in the whole cohort.

Conclusion: All the findings suggest that 5-HT2A participates in human spatial cognitive abilities and spatial working memory.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/s0317167100011513DOI Listing
March 2011