The association of CLOCK gene T3111C polymorphism and hPER3 gene 54-nucleotide repeat polymorphism with Chinese Han people schizophrenics

Many reports have shown that the biologic rhythm could be altered due to mutations of circadian gene hClock or hPeriod, and the mutations of circadian genes have some relationship with psychosis according to recent studies. A preliminary study has been conducted to examine wether the T3111C single nucleotide polymorphism of the hClock gene or the length polymorphism of the hPer3 gene is associated with the development of schizophrenia. The samples from schizophrenics (n = 148, male: 57.4%, female: 42.6%) and normal controls (n = 199, male: 59.3%, female: 40.7%) were examined. Allele frequencies of T3111C SNP of hClock were significantly different between schizophrenics and controls (χ² = 19.738, P < 0.05). Schizophrenics had a significantly higher frequency of the C allele compared with controls (OR = 2.613, 95% CI = 1.693–4.034). On the other hand, there is no significant difference of allele frequencies of 18 exon of hper3 between schizophrenics and controls (χ² = 0.192, P > 0.05). Our results suggest that the T3111C (RS1801260) polymorphism of hClock gene is associated with schizophrenia, but it seems that the length polymorphism of 18 exon of hPer3 may not be associated with schizophrenia. It is important to address of the relationship between circadian gene polymorphisms and dopamine functions in further study.     

Association of Per3 length polymorphism with susceptibility of Alzheimer disease (AD) in Chinese population

Objectives: The association of Per3 length polymorphism with susceptibility of Alzheimer Disease (AD) was examined in the present study. Methods: This study was constructed using the case-control method and investigated the association of Per3 length polymorphism with susceptibility of AD. Genotypes of APOE and Per3 length were determined by a PCR restriction fragment length polymorphism detection method. Results: In this study, we gathered 130 unrelated AD patients and 188 controls in performing an analysis the association of Per3 length polymorphism with susceptibility of AD. In the whole sample or APOE ε4 non-carriers, an increased prevalence of five repeat homozygotes of Per3 length in AD patients had significant higher than that in controls (in the whole sample: χ² = 7.261,= 0.0176; in APOE ε4 non-carriers: χ² = 6.086, p = 0.030). And, among APOE ε4 carriers, an increased prevalence of five repeat homozygotes of Per3 length in AD patients had also significant higher than that in controls (χ² = 3.893, p = 0.0319). Conclusions: Among APOE ε4 non-carriers, five repeat homozygotes of Per3 length was associated with a high susceptibility of AD among APOE ε4 carriers and non-carriers.     

Association of BDNF gene polymorphism with bipolar disorders in Han Chinese population

Recent data suggest that brain‐derived neurotrophic factor (BDNF) plays an essential role in neuronal plasticity and etiology of bipolar disorders (BPD). However, results from different studies have been inconsistent. In present study, 342 patients who met DSM‐IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) criteria for bipolar disorders type I (BPD‐I) or type II (BPD‐II) and 386 matched health controls were enrolled, and TaqMan® SNP Genotyping Assays (Applied Biosystems, Foster City, CA, USA) were applied to detect the functional polymorphism rs6265 (Val66Met) of BDNF gene. Treatment response to lithium and valproate was retrospectively determined. The association between Val66Met polymorphism and BPD, treatment response to mood stabilizers, was estimated. The genotype and allele distribution of Val66Met polymorphism between BPD patients and control subjects showed significant difference (genotype: χ² = 6.18, df = 2, P = 0.046; allele: χ² = 5.01, df = 1, P = 0.025) with Met allele as risk factor for disease susceptibility (OR = 0.79, 95%CI as 0.64–0.97). The post hoc analysis interestingly showed that Met allele had opposite effect on the treatment response for BPD‐I and BPD‐II separately. For BPD‐I patients, the response score in Val/Val group was significantly lower than that in Met allele carriers (t = ?2.27, df = 144, P = 0.025); for BPD‐II patients, the response score in Val/Val group was significantly higher than that in Met allele carriers (t = 2.33, df = 26, P = 0.028). Although these results should be interpreted with caution because of the limited sample for Val/Val genotype in BPD‐II patients (N = 5), these findings strengthen the hypothesis that BDNF pathway gets involved in the etiology and pharmacology of BPD and suggest the differences between BPD‐I and BPD‐II.     

Association of TNFAIP3 polymorphism with rheumatic heart disease in Chinese Han population

In a pair-matched case–control study (239 versus 478) conducted in Chinese Han population, we investigated the association between tumor necrosis factor-α-induced protein 3 (TNFAIP3) gene, tumor necrosis factor receptor-associated factor 1 (TRAF1) gene, complement component 5 (C5) gene, and rheumatic heart disease (RHD). We observed no association with RHD for the five tagging single nucleotide polymorphisms (tSNP) in the C5 gene, the three tSNPs in the TNFAIP3 gene, or the two tSNPs in the TRAF1 gene. However, we determined that the tSNP, rs582757, located at intron_5 of the TNFAIP3 gene, associated with RHD in Chinese Han population. Both the distribution of genotype and allele frequencies differed significantly between case and control subjects (p?=?0.001 and p?=?0.0004, respectively). The minor C allele reduced the risk of RHD with a per-allele odds ratio of 0.57 (0.42–0.78) for the additive model in univariate analysis (p?=?0.000). Under a dominant model, CC/CT carriers had a 0.54-fold reduced risk of RHD (95% confidence interval 0.38–0.75, p?=?0.000) than TT carriers. Therefore, we report a new genetic variant (rs582757) in the TNFAIP3 gene that associated with the prevalence of RHD in Chinese Han population. Further genetic and functional studies are required to identify the etiological variants in linkage disequilibrium with this polymorphism.     

云南汉族人群5-羟色胺转运体基因启动子区多态性与酒精依赖的相关性

为了探讨云南汉族人群中5-羟色胺转运体基因启动子区多态性(5-HTTLPR)与酒精依赖的关联性, 文章采用PCR扩增和DNA测序技术, 对云南地区118例酒精依赖患者和214例健康对照个体进行了5-HTTLPR的基因多态性分析。结果表明: 酒精依赖患者组和正常对照组的5-HTTLPR的基因型分布存在显著性差异, L/L和L/S基因的携带者人群嗜酒发生率显著低于S/S基因型人群(OR: 0.581, P=0.026)。S和L等位基因频率在两组间无统计学差异(χ²=2.594, P=0.107), 但其分布存在种族差异性。因此, 云南地区人群中5-HTTLPR多态与酒精依赖存在相关性, L/L和L/S基因型可能是降低酒精依赖发病的影响因子之一。     

Higher scores in the extraversion personality trait are associated with a functional polymorphism in the PER3 gene in healthy subjects

A polymorphism in the PER3 (period circadian clock 3) gene has been associated with neuropsychiatric disorders and endophenotypes. We evaluated the possible association of personality domains with the PER3 polymorphism in a sample of healthy subjects: 271 individuals were evaluated with the Big Five Inventory and genotyped for the PER3 Variable Number Tandem Repeat (VNTR) polymorphism. We found a significant association between the PER3 polymorphism and the extraversion personality trait (p = 0.0093). The 5/5 genotype carriers showed higher scores for extraversion. This is the first time that a significant association between the PER3 VNTR polymorphism and extraversion is reported.     

北京汉族群体39个短串联重复序列基因座多态性及其遗传关系

本文首次对北京地区汉族人群的13个CODIS(Combined DNA index system)和26个非CODIS系统STR基因座的遗传多态性进行了研究,建立了北京地区汉族人群39个STR基因座的群体遗传多态性数据库并对其法医学应用价值进行了评价。39个STR基因座的基因型分布均符合Hardy-Weinberg平衡且各基因座之间均不存在连锁现象,个体鉴别力(Power of discrimination, DP)在0.7740~0.9818之间,期望杂合度(Expected heterozygosity, He)在0.6000~0.9350之间,多态性信息含量(Polymorphism information content, PIC)在0.5317~0.9047之间,非父排除率(Power of exclusion, PE)在0.2909~0.8673之间,累积个体鉴别力(Cumulative probability of discrimination, CDP)为0.999999999999999999999999999999999999999964971,累积非父排除率(Cumulative probability of exclusion, CPE)为0.999999999973878。另外,结合已公开报道的国内其他11个群体相应基因座的遗传资料,根据等位基因频率计算遗传距离,构建了系统发生树。本研究可为中国法医DNA数据库和群体遗传学数据库提供重要的基础数据,对北京地区汉族人群开展法医学个体识别、亲权鉴定和遗传学研究具有重要的意义。     

CNR1、GAD1和BDNF基因多态性与云南傣族男性海洛因依赖的相关性分析

为了探讨大麻素受体1基因(Cannabinoid receptor 1,CNR1)3个SNP位点(rs6454674、rs1049353和rs806368)、谷氨酸脱羧酶1基因(Glutamate decarboxylase 1,GAD1)3个SNP位点(rs1978340、rs3791878和rs11542313)、脑源性神经营养因子基因(Brain-derived neurotrophic factor,BDNF)2个SNP位点(rs6265和rs13306221)与云南傣族男性海洛因依赖的相关性,文章采用病例对照关联分析,建立8-SNPs复合扩增体系,应用SNaPshot方法检测165例傣族男性海洛因依赖患者和170例健康傣族男性CNR1、GAD1和BDNF基因8个SNPs位点基因型,采用SPSS17.0、Haploview4.2、PHASE2.1和MDR软件进行统计学分析。结果显示,rs13306221基因型频率在海洛因依赖组和对照组中的差异具有统计学意义(P<0.025),海洛因依赖组rs6265 A等位基因显著高于对照组(P<0.05),由rs1978340-rs3791878-rs11542313构建的T-A-C、C-C-C、C-C-T和T-C-C单体型及rs6265-rs13306221构建的A-G单体型频率在海洛因依赖组及对照组中差异具有统计学意义(P<0.05),海洛因依赖组T-A-C、C-C-T和A-G单体型频率明显高于对照组,GAD1基因rs1978340与rs3791878之间可能存在强协同的交互作用。结果表明,CNR1基因rs1049353多态性、GAD1基因rs1978340和rs11542313多态性以及BDNF基因rs6265和rs13306221多态性与云南傣族男性海洛因依赖相关联,并且携带rs6265 A等位基因的个体可能更容易对海洛因产生依赖。     

Association study of CRP gene polymorphism and hypertension in Han Chinese population

Background

Serum C-reactive protein (CRP) and genetic variation of CRP gene have been reported as a strong, independent predictor of myocardial infarction and stroke. But there is rare association evidence of CRP genetic variation and hypertension (HT).

Methods

A community-based case–control study including 1331 cases with HT and 1400 controls was used to evaluate the association of tagSNPs covered CRP gene, CRPP1 gene and 40 kb upstream with HT in a Chinese Han population. Haplotypes and stratification analysis were applied to further evaluate relationships between the screened SNPs and HT and general linear model (GLM) was applied to compare blood pressure levels between genotypes.

Results

In stage 1, five SNPs had positive association with HT (P < 0.05) and entered stage 2 and two SNPs rs876537 and rs10737175 polymorphisms showed significant association with HT in joint sample. Haplotype analysis showed that comparing with common haplotype T–C which was constructed by rs6677719 and rs10737175, haplotype T–T significantly associated with HT after adjusted covariates. Stratification analysis found significant associations of HT for rs876537, rs2808630, rs6677719 and rs10737175 in ≥ 50 years group, rs876537, rs10737175 in female, rs876537 and rs10737175 in non-smoking and non-drinking populations as well as rs2808630 in non-drinking population. Furthermore, quantitative trait analysis indicated significant differences of SBP and DBP between the genotypes of rs10737175, rs876537 and rs2808630 in non-treatment hypertensive cases and control population.

Conclusions

The findings of this study support that CRP gene polymorphisms have significant association with genetic susceptibility of HT and quantitative traits of blood pressure.     

Association study of AGER gene polymorphism and hypertension in Han Chinese population

Background

Advanced glycation end products (AGEs) are produced by non-enzymatic glycation or glycoxidation of proteins, lipids and nucleic acids. The bond of AGEs and the receptor of AGE (AGER) in a pro-oxidant environment could induce immune and inflammation reaction involved in progress of microvascular disease. Accumulated evidence warrant further study on AGE–AGER pathway and genetic susceptibility to hypertension (HT).

Methods

We designed a two-stage association study to evaluate the association of AGER polymorphism and HT. In stage 1, seven tagSNPs were tested in 524 cases and 531 controls and the significant SNPs (P < 0.05) would enter into stage 2 including 807 cases and 869 controls. Furthermore, joint analysis was performed for all 2731 subjects including 1331 cases and 1400 controls, and meta-analysis was applied to evaluate combined estimations from the subgroups of stage 1 and stage 2.

Results

In stage 1, rs204994 had significant association with HT (P < 0.05) and enter stage 2. Neither joint analysis nor meta-analysis found statistical association of rs204994 with HT after adjusted for the covariates in the whole population. However, further stratification analysis found that rs204994 was significantly associated with HT in < 50 years and ≥ 50 years groups, ORs (95%CI) of dominant model were 1.623 (1.054–2.500) and 0.721 (0.546–0.952) respectively. No significant correlation was found between blood pressure and the polymorphisms of rs204994.

Conclusions

Our data suggests that age might modulate the genetic effects of variation of rs204994 in AGER on HT and further replications in other populations and functional studies should be warranted.     

Association of NRG3 and ERBB4 gene polymorphism with nicotine dependence in Turkish population

Background

Nicotine dependence (ND) is characterized by regular smoking, anxiety, irritation, difficulty concentrating, impatience, restlessness, tremor, dizziness, hunger, nicotine demand, and the individual’s reluctance to quit despite knowing the health risks of smoking. Recently, it has been reported that the Neuregulin 3 (NRG3)/Erb-B2 receptor tyrosine kinase 4 (ERBB4) signaling pathway plays a role in ND. NRG3, which is activated after nicotine intake, binds to ERBB4 and causes GABA release. GABA reduces anxiety and tension, which are one of the nicotine withdrawal symptoms. Therefore we aimed to investigate the relationship between NRG3 and ERBB4 gene polymorphisms and ND.

Materials and methods

The study population was comprised of patients with ND (n?=?200) and healthy non-smoker control subjects (n?=?200) who were matched for age, sex, and compared for comorbidity factors such as alcohol, smoking, duration, and education (age range 18–60). Genotypes were detected by Real-Time PCR using TaqMan technology. The Fagerström Nicotine Dependence Test (FTND) score was 5 and above for the patient group and 0 for the control group. DNA was obtained from whole peripheral blood and six polymorphisms of Neuregulin 3 (NRG3) (rs1836724, rs7562566, and rs10048757) and Erb-B2 Receptor Tyrosine Kinase 4 (ERBB4) (rs1764072, rs6584400, and rs10883934) genes were analyzed by real-time PCR method.

Results

Our findings show that the six selected SNPs are not significantly associated with ND in the Turkish population and no correlation with dependence levels (p?>?0.05).

Conclusion

Although our findings do not show a relationship between ND and these polymorphisms, it is the first study to investigate these single nucleotide polymorphisms (SNPs) for the first time in ND and to find some genotypes in the Turkish population when compared to other populations. Also, our findings are important in terms of their contribution to the literature and forensic genetics.

     

Association of the carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase gene with schizophrenia in the Chinese Han population

Several independent linkage studies have demonstrated that the 1q22 region is likely to harbor candidate schizophrenia susceptibility genes. Recently, some genetic variants within CAPON have been reported as exhibiting significant linkage disequilibrium to schizophrenia in Canadian familial-schizophrenia pedigrees. We examined nine single nucleotide polymorphisms (SNPs), which span an approximately 236-kb region of CAPON, in 664 schizophrenia cases and 941 controls in the Chinese Han population. We detected a significant difference in allele distributions of SNP rs348624 (P = 0.000017). Moreover, the overall frequency of haplotypes constructed from three SNPs including rs348624 showed significant difference between cases and controls (P = 0.000025). Our findings indicate that CAPON gene may be a candidate susceptibility gene for schizophrenia in Chinese Han population, and also provide further support for the potential importance of NMDAR-mediated glutamatergic transmission in the etiology of schizophrenia.     

Association of the CTLA-4 +49A/G polymorphism with rheumatoid arthritis in Chinese Han population

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is an important molecule in the regulation of T cells, so the CTLA-4 gene has been considered as a strong candidate associated with T cell-mediated autoimmune diseases such as rheumatoid arthritis (RA). CTLA-4 has many variants and polymorphic forms, among which the +49A/G polymorphism, causing a non-synonymous substitution, has been studied most. However, previous studies of the association between the +49A/G polymorphism of the CTLA-4 gene and RA have provided conflicting results. The aim of this study was to determine the potential relationship of the CTLA-4 +49A/G polymorphism and the risk of RA in Chinese Han population. TaqMan assay was used to genotype the +49A/G polymorphism in 1,489 RA patients and 1,200 healthy controls. Furthermore, a meta-analysis of all studies relating this polymorphism in Chinese population to the risk of RA was performed. The genotype and allele frequencies of the CTLA-4 +49A/G in patients with RA differed significantly from those of controls (P = 0.03 and P = 0.007, respectively). The meta-analysis also revealed that the CTLA-4 +49G allele was associated with an increased risk of RA in Chinese population. Our results suggested that the CTLA-4 gene might contribute to the pathogenesis of RA, and the +49A/G polymorphism of this gene was a risk factor associated with increased RA susceptibility in Chinese Han population.     

Neither single‐marker nor haplotype analyses support an association between the dopamine transporter gene and heroin dependence in Han Chinese

Much evidence suggests that dysfunction of dopamine transporter‐mediated dopamine transmission may be involved in the pathophysiology of substance abuse and dependence. The aim of this study was to examine whether the dopamine transporter gene (DAT1; SLC6A3) is associated with the development of heroin dependence (HD) and whether DAT1 influences personality traits in patients with HD. Polymorphisms of DAT1 were analyzed in a case–control study of 1046 Han Chinese (615 patients and 431 controls). All participants were screened using a Chinese version of the modified Schedule of Affective Disorder and Schizophrenia‐Lifetime and all patients met the criteria for HD. Furthermore, a Chinese version of the Tridimensional Personality Questionnaire (TPQ) was used to assess personality traits in the patient group and examine the association between their personality traits and DAT1 polymorphisms. Of the patient group, 271 completed the TPQ. No statistically significant differences in allele or genotype frequencies of all investigated variants between HD patients and controls were observed. In haplotype analyses, four haplotype blocks of DAT1 were not associated with the development of HD. These DAT1 polymorphisms did not influence novelty seeking and harm avoidance scores in HD patients. This study suggests that the DAT1 gene may not contribute to the risk of HD and specific personality traits in HD among the Han Chinese population.     

Association of the D repeat polymorphism in the ASPN gene with developmental dysplasia of the hip: a case-control study in Han Chinese

Introduction

Developmental dysplasia of the hip (DDH) is a common skeletal disease, which is characterized by abnormal seating of the femoral head in the acetabulum. Genetic factors play a considerable role in the etiology of DDH. Asporin (ASPN) is an ECM protein which can bind to TGF-β1 and sequentially inhibit TGF-β/Smad signaling. A functional aspartic acid (D) repeat polymorphism of ASPN was first described as an osteoarthritis-associated polymorphism. As TGF-β is well known as an important regulator in the development of skeletal components, ASPN may also be involved in the etiology of DDH. Our objective is to evaluate whether the D repeat polymorphism of ASPN is associated with DDH in Han Chinese.

Methods

The D repeat polymorphism was genotyped in 370 DDH patients and 445 control subjects, and the allelic association of the D repeat was examined.

Results

From D11 to D18, eight alleles were identified. D13 allele is the most common allele both in control and DDH groups, the frequencies are 67.3% and 58.1% respectively. In the DDH group, a significantly higher frequency of the D14 allele and significantly lower frequency of D13 was observed. The association of D14 and D13 was found in both females and males after stratification by gender. There was no significant difference in any other alleles we examined.

Conclusions

Our results show an obvious association between the D repeat polymorphism of ASPN and DDH. It indicates that ASPN is an important regulator in the etiology of DDH.     

RELN基因启动子区SNP位点与精神分裂症的相关性分析

目前有很多证据证明RELN基因在世界人群中是一个精神分裂症的致病基因.基于之前报道过的RELN基因在精神分裂症患者中表达下降的事实,可以推测在RELN基因启动子区可能包含影响精神分裂症发生的多态位点.该研究分析了中国西南地区病例——对照人群中(940位患者和1369位正常人)RELN基因启动子区的3个单核苷酸多态性位点与精神分裂症的相关性.研究结果显示,这些多态位点都不与精神分裂症相关,表明RELN基因的致病位点并不在其启动子区.将前人研究结果与该研究结果进行综合分析(共2843个样本),结果仍不显著.因此,该研究表明,RELN基因启动子区的单核苷酸多态性位点在中国人群中并不与精神分裂症相关.