Interactions between four gene polymorphisms and their association with patients with Parkinson's disease in a Chinese Han population

The four previously reported Parkinson's disease (PD)-related single-nucleotide polymorphisms (SNPs) – rs1775143, rs823114, rs2071746 and rs62063857 – have rarely been studied in Chinese Han populations. To examine the association between these SNPs and PD, we conducted a case-control study of 158 patients with PD and 210 controls. All participants were Chinese Han from Northern China. With covariate adjustment for clinical characteristics, logistic regression analysis revealed no differences in genotype or allele frequencies for the four SNPs. Stratified by age of disease onset, sex, smoking status, duration of disease, baseline UPDRS, Hoehn–Yahr Stage, PD subtypes, scores of Hamilton anxiety scale, Hamilton depression scale and activity of daily living, all of the p values did not remain significant after Bonferroni correction. However, the haplotype rs1775143T-rs823114G-rs2071746T-rs62063857A was associated with increased risk of developing PD (p = 0.003, OR = 456.88, 95% CI: 27.40–7619.75) in our case-control sample set. The haplotype rs1775143T-rs823114G-rs2071746T was also associated with increased risk of developing PD (p = 0.003, OR = 338.43, 95% CI: 20.68–5538.27). Although the haplotype rs1775143T-rs823114G-rs62063857A was associated with increased risk of PD (p = 0.03), the 95% CI was 0.993–22.469. Our data demonstrate that although specific SNPs were not related with PD patients, certain haplotypes were associated with increased risk for PD in the Chinese Han population. These results provide further evidence that the etiology of PD is multifactorial, although the underling mechanism needs further study.     

Associations between oxytocin receptor gene (OXTR) polymorphisms and self-reported aggressive behavior and anger: Interactions with alcohol consumption

Oxytocin has been implicated in the regulation of social as well as aggressive behaviors, and in a recent study we found that the effect of alcohol on aggressive behavior was moderated by the individual's genotype on an oxytocin receptor gene (OXTR) polymorphism (Johansson et al., 2012). In this study we wanted to deepen and expand the analysis by exploring associations between three (rs1488467, rs4564970, rs1042778) OXTR polymorphisms and aggressive behavior, trait anger as well as anger control in a population-based sample of Finnish men and women (N=3577) aged between 18 and 49 years (M=26.45 years, SD=5.02). A specific aim was to investigate if the polymorphisms would show interactive effects with alcohol consumption on aggressive behavior and trait anger, as well as to explore whether these polymorphisms affect differences in anger control between self-reported sober and intoxicated states. The results showed no main effects of the polymorphisms, however, three interactions between the polymorphisms and alcohol consumption were found. The effect of alcohol consumption on aggressive behavior was moderated by the genotype of the individual on the rs4564970 polymorphism, in line with previous results (Johansson et al., 2012). For trait anger, both the rs1488467 and the rs4564970 polymorphisms interacted with alcohol consumption. It appears that the region of the OXTR gene including both the rs4564970 and the rs1488467 polymorphisms may be involved in the regulation of the relationship between alcohol and aggressive behavior as well as between alcohol and the propensity to react to situations with elevated levels of anger.     

Association of EPHB1 rs11918092 and EFNB2 rs9520087 with psychopathological symptoms of schizophrenia in Chinese Zhuang and Han populations

Two single‐nucleotide polymorphisms (SNPs) (rs11918092 and rs9520087) were genotyped in Chinese Zhuang and Han populations. Symptoms of schizophrenic patients were assessed by the Positive and Negative Syndrome Scale. No association of any SNP with schizophrenic susceptibility was found. However, associations of rs9520087 with the total scale score (P = 0.014), positive scale score (P = 0.013), negative scale score (P = 0.032), and general psychopathology scale score (P = 0.031) were found in Zhuang patients. Additionally, rs11918092 was associated with positive scale score (P = 0.035) in Han patients. The two SNPs might influence symptoms of schizophrenia.     

MicroRNA相关基因Dicer rs1057035多态性与脑胶质瘤的相关性研究

目的探讨陕西地区汉族人群中,Dicer基因rs1057035多态性与脑胶质瘤的相关性。方法 200例陕西地区脑胶质瘤患者作为病例组,随机选择同期在我科住院治疗的非肿瘤疾病患者184例作为对照组,收集所有入住患者相关临床资料,并采用聚合酶链反应-限制性内切酶分析(PCR-RFLP)法检测Dicer基因rs1057035单核苷酸多态性。结果病例组患者Dicer基因rs1057035位点等位基因C分布频率明显低于对照组(χ~2=5.137,P=0.023)。分层分析,携带突变等位基因C可降低酗酒者,无肿瘤性疾病家族史者以及Ⅲ型、Ⅳ型胶质瘤患者发病风险(OR=0.253,95%CI 0.067～0.949,P=0.036;OR=0.561,95%CI 0.339～0.930,P=0.024;OR=0.525,95%CI 0.284～0.969,P=0.037)。结论 Dicer基因rs1057035多态性可能与脑胶质瘤遗传易感性相关。     

α-突触核蛋白基因多态性与汉族帕金森病患者病情进展的相关性研究

目的探讨α-突触核蛋白基因rs11931074位点多态性与帕金森病患者病情进展的相关性。方法采用病例对照研究方法,选取2014年3月至2017年10月在南京脑科医院就诊的帕金森病患者154例(PD组)及健康体检志愿者194例(对照组)为研究对象,采用MassARRAY■SNP方法对SNCA基因rs11931074位点多态性进行分析,分别在患者基线及随访(3年)时间点进行UPDRS、HAMD、HAMA、PDNMSQ、PDSS、MMSE等相关量表评估,计算差值年限比(即基线及随访时差值/年限),分析基因rs11931074多态性与帕金森病病情进展的相关性。结果与对照组比较,PD组rs11931074T等位基因、TT基因型变异频率高干对照组(P=0.01);线性相关分析示rs11931074变异(GT+TT)携带者发病年龄越大,日常生活能力损害越严重(P=0.03);多因素线性回归分析示SNCA基因rs11931074位点与PD患者强直症状进展相关(P=0.036);SNCA基因rs11931074TT基因型与PD患者强直症状进展相关(P=0.03)。结论SNCA基因rs11931074位点多态性与帕金森病病情进展相关;rs11931074 TT基因型与帕金森病强直症状进展相关,随着病程进展基因rs11931074变异(GT+TT)携带者日常生活能力损害更严重。     

Quantitative assessment of the effect of FGF20 rs12720208 variant on the risk of Parkinson’s disease: a meta-analysis

Objectives: Many studies have investigated the association between fibroblast growth factor 20(FGF20) rs12720208(C/T) polymorphism and the susceptibility of Parkinson’s disease (PD). However, published data are still controversial. Here, we performed a meta-analysis to evaluate the association of rs12720208 polymorphism with the risk of PD.

Methods: Up to April 2016, Pubmed, EMbase, Web of science, the Chinese National Knowledge Infrastructure, and Wanfang Medicine were reviewed to identify appropriate documents. A total of seven papers involving 11 studies with 3360 PD cases and 3681 controls were included based on the strict inclusion and exclusion standards. And STATA 12.0 statistics software was used to calculate available data from each study. The pooled odds ratios (OR) and 95% confidence interval (CI) were calculated to assess the association between FGF20 rs12720208 polymorphism and PD risk.

Results: When all studies were pooled into this meta-analysis, neither the minor T allele frequencies nor the genotypic distributions were different between PD cases and controls. But the subgroup analysis stratified by ethnicity showed FGF20 rs12720208 polymorphism was associated with increased risk in the allele model (T vs. C:OR = 1.167, 95% CI = 1.020–1.335) and dominant model (TT + TC vs. CC:OR = 1.156, 95% CI = 1.001–1.335) in Caucasians but not in Asians.

Conclusions: This meta-analysis indicates that rs12720208 C/T variant might be associated with PD susceptibility in Caucasians.     

H63D polymorphism in the hemochromatosis gene is associated with sporadic amyotrophic lateral sclerosis in China

Background and purpose: The H63D polymorphism in the hemochromatosis (HFE) gene has been reported as a risk factor for amyotrophic lateral sclerosis (ALS) in Europe and America, but no data have been reported for Asia. Here, we investigated the possible association between H63D and sporadic ALS (sALS) in a Chinese Han population. Methods: A total of 195 individuals with sALS from three centers in China and 405 unrelated healthy controls were recruited. All subjects were genotyped by restriction fragment length polymorphism (RFLP) analysis. Results: Sporadic ALS was significantly related to the H63D polymorphism in heterozygous carriers (odds ratio 3.10, 95%CI: 1.49–6.47, P = 0.002). Conclusions: The HFE H63D polymorphism may contribute to the development of sALS in Chinese.     

No association between a polymorphism of the adenylate cyclase type IX gene and major depressive disorder in the Chinese Han population

Previous studies have demonstrated that a missense single-nucleotide polymorphism variant (2316A>G;rs2230739)of the adenylate cyclase type IX gene was associated with bipolar disorder and affective disorder.We determined genotype and allele frequencies using a ligase detection reaction method in 315 patients with major depressive disorder and 278 unrelated, sex-matched healthy control subjects.We did not detect any statistically significant differences in genotype and allele frequencies between patients and healthy control subjects.Furthermore,we found no significant difference between genders in major depressive disorder,nor between patients and controls in the same gender.These results suggest that 2316A>G(rs2230739)may not be a risk factor for increasing susceptibility to major depressive disorder in the Chinese Han population.     

难治性精神分裂症与亚甲基四氢叶酸还原酶基因多态性的关联分析

目的:探讨难治性精神分裂症与亚甲基四氢叶酸还原酶(MTHFR)基因C677T和A1298C多态性的关系。方法:应用聚合酶链反应-限制性片断长度多态性方法(PCR-RFLP)检测102名正常对照、138例难治性精神分裂症患者及97例非难治性精神分裂症患者MTHFR基因的C677T和A1298C多态性。结果:患者组与对照组,难治组与非难治组C677T、A1298C基因型分布差异均无统计学意义(C677T,χ2=4.83,P=0.09;χ2=1.90,P=0.39;A1298C,χ2=1.50,P=0.47;χ2=3.90,P=0.14),而患者组C677T的T等位基因频率显著高于正常对照组(P=0.04),难治组A1298C的C等位基因频率显著高于非难治组(P=0.04)。677TT/1298AA、677CT/1298AC复合基因型患病相对风险度比677CC/1298AA型显著提高(OR=4.13,95%CI=1.26～13.58,P=0.02;OR=2.95,95%CI=1.23～7.07,P=0.01),而在难治组和非难治组中,复合基因型差异无统计学意义。结论:MTHFR基因677T等位基因和677TT/1298AA、677CT/1298AC复合基因型是精神分裂症发病危险因素,MTHFR基因1298C等位基因可能是难治性精神分裂症的危险因子之一。     

C-reactive protein gene polymorphisms and gene-environment interactions in ischaemic stroke

Abstract

Ischaemic stroke is a heterogeneous, multifactorial disease caused by the combination of certain risk factors and genetic factors. Several single nucleotide polymorphisms (SNPs) of C-reactive protein (CRP) have been reported to be associated with serum CRP levels. However, genetic association studies have produced conflicting results regarding the association between these SNPs and ischaemic stroke. In this paper, we conducted a population-based case-control study to determine whether two SNPs of CRP (rs1800947 and rs3093059) are associated with ischaemic stroke in Chinese Han population and to evaluate their interaction with environmental risk factors. We found that the rs1800947 GC genotype is significantly associated with the risk of ischaemic stroke, particularly the small-vessel disease and its subtype. Crossover analysis revealed that patients with the rs1800947 GC genotype and habits of smoking or drinking were more susceptible to ischaemic stroke. No association was found between the rs3093059 and ischaemic stroke.     

A GWAS-supported variant interacting with diabetes predicts risk of atherothrombotic stroke in Han Chinese population

Background: A recent genome-wide association study has identified that rs4376531 variant conferred risk of atherothrombotic stroke (AS) in a Japanese population. This study was to explore the association in Han Chinese population.

Methods: A total of 1036 cases and 643 healthy controls were enrolled. We genotyped rs4376531 variant with SNPscan. Multivariate logistic regression analysis was used to determine the association of genetic variation with risk of AS. Interaction analysis was examined by SNPStats web tool.

Results: After adjusting for gender, age, body mass index (BMI), hypertension, diabetes and smoking, compared with CC genotype, we observed that GC and GG/GC genotypes were associated with a significantly decreased risk of AS (OR?=?0.76, 95% CI?=?0.58–0.99 and OR?=?0.76, 95% CI?=?0.58–0.98, respectively). The decreased risk was more obvious among subgroups with high BMI (OR?=?0.63, 95% CI?=?0.45–0.88), no hypertension (OR?=?0.66, 95% CI?=?0.46–0.94), diabetes (OR?=?0.33, 95% CI?=?0.17–0.64), and smoking (OR?=?0.65, 95% CI?=?0.44–0.95) in the dominant model (GG/GC vs CC). Interaction analysis also revealed that compared with non-diabetic patients with CC genotype, diabetic patients with CC genotype had a 4.48-fold (OR?=?4.48; 95% CI?=?2.98–6.72) increased risk of AS.

Conclusion: Our data suggested that GC and GG/GC of rs4376531 contributed to a decreased risk of AS while CC genotype, interacting with diabetes, increased the stroke risk in Han Chinese population.     

中国新疆维吾尔族人群中ANK3基因rs10761482多态性与精神分裂症关联性的病例对照研究(英文)

背景:ANK3基因rs10761482多态性已被发现与精神分裂症的发生相关联。目的:评估新疆维吾尔族人群ANK3基因和精神分裂症之间的关联。方法:使用Taqman探针技术对630例新疆维吾尔族精神分裂症患者和535名新疆维吾尔族健康人群进行ANK3基因rs10761482位点的基因分型。采用SHEsis和SPSS17.0软件进行数据分析。结果:病例组和对照组之间的基因型和等位基因频率无显著差异。在病例组,性别或精神分裂症发病年龄与基因型或等位基因频率之间没有显著关联。将男性和女性单独分析,病例组与对照组之间的等位基因和基因型频率均未发现显著差异,青春期发病与成年后发病的精神分裂症患者之间的等位基因和基因型频率也无显著差异。结论:我们的研究结果不支持以往ANK3基因与精神分裂症有关联的报告。本研究招募的维吾尔族人群中,ANK3基因rs10761482多态性与精神分裂症之间没有显著关联。如果这些结果在进一步的研究中得到证实,那么研究重点将转而了解为什么在这个特定的族群中不存在上述已经被广泛认可的关联。     

Dopamine D2 (DAD2) and dopamine D3 (DAD3) receptor gene polymorphisms and treatment outcome in alcohol dependence

Summary. The dopaminergic system is critically involved in reward mechanisms mediating the reinforcing effects of alcohol. The intention of this study was to investigate the genotypic frequencies of the −141C Ins/Del polymorphism of the DAD2 receptor gene as well as the Bal I polymorphism of the DAD3 receptor and their potential association with treatment outcome in alcoholism. Therefore, individuals suffering from primary alcohol dependence were clinically and genetically characterized and followed prospectively over a period of one year after inpatient treatment. No association was found between DAD2 or DAD3 receptor gene variants and treatment outcome as reflected by abstinence/relapse after one year. Taking into account potential stratification effects, such as family history, gender, age of onset, or severity of the disease an association with DAD2 or DAD3 gene variants could neither be found. In conclusion, we found no evidence that the DAD2 or DAD3 gene variants investigated have a major influence on treatment outcome in primary alcohol dependence. Received June 2002; accepted February 3, 2003 Published online April 22, 2003 RID="*" ID="*"  This paper is dedicated to Prof. Peter Riederer who celebrated his 60^th birthday in March 2002 Authors' address: PD Dr. G. A. Wiesbeck, Addiction Research Group, Psychiatric Clinic, University of Würzburg, Füchsleinstrasse 15, D-97080 Würzburg, Germany, e-mail: wiesbeck_g@klinik.uni-wuerzburg.de     

磷酸二酯酶4D基因与缺血性脑卒中的研究进展

磷酸二酯酶4D（PDE4D）在人体组织中广泛分布,其活性受环腺苷酸（cAMP）依赖的蛋白激酶（PKA）和细胞外信号调节激酶（ERK）调节。PDE4D基因包含1．6Mb,含24个外显子,编码9种蛋白质亚型和至少7个启动子。磷酸二酯酶4D降解cAMP,通过改变cAMP活性,促进动脉粥样硬化形成从而引起缺血性脑卒中发生。PDE4D基因多态性研究,为防治缺血性脑卒中提供了一条重要途径。     

5-羟色胺2A受体基因多态性与利培酮治疗中国首发精神分裂症患者疗效关联

背景5-羟色胺2A受体基因已经证实为精神分裂症的候选易感基因,因为阐明其作为非典型抗精神病药物重要作用靶点减轻阴性症状已引起业界倍加关注.本研究试图探讨(1)5-HT2A受体基因T102C多态性在不同临床亚型之间等位基因和基因型频率的关系,(2)5-HT2A受体基因T102C在利培酮高剂量组和低剂量组之间基因型和等位基因分布频率的关系,(3)5-HT2A受体基因T102C多态性在治疗有效组与无效组之间的基因型和等位基因分布频率的关系,(4)5-羟色胺2A受体T102C基因多态性是否与中国首发精神分裂症患者利培酮疗效有关.方法对201例精神分裂症初发期患者分别进行利培酮治疗[3～5 mg/d,平均(3.2±1.3)mg/d],疗程8周.采用聚合酶链式反应扩增与限制性片段长度多态性(PCR-RFLP)技术检测5-HT2A受体基因T102C多态性.以临床亚型将精神分裂症患者划分为偏执型、瓦解型、未定型和其他型,分析不同临床亚型等位基因和基因型频率的差异;按服用利培酮剂量划分低剂量组(＜4 mg/d)和高剂量组(≥4 mg/d),经比较利培酮高剂量组和低剂量组的5-HT2A受体基因T102C基因型和等位基因分布频率差异性;同时以阴性和阳性症状量表(PANSS)总减分率＞50%有效,≤50%为无效以分析治疗有效组与无效组之间的基因型和等位基因分布频率差异有无显著性;以PANSS评定患者治疗前及治疗后2周、4周、6周和第8周末的精神症状,比较5-HT2A受体T102C各基因亚型与年龄、发病年龄、PANSS总分值、阳性症状基线分、阴性症状基线分、一般病理症状基线分、PANSS总减分率、阳性症状减分率、阴性症状减分率和一般病理症状减分率的差异.结果5-HT2A受体T102C基因型在患者组分布频率均符合H-W平衡定律(P＞0.05);不同临床诊断亚型精神分裂症患者等位基因和基因型频率无显著性差异(χ2=0.415,P=0.937;χ2=1.705,P=0.941);高剂量组与低剂量组之间的基因型和等位基因分布频率差异均无显著性(χ2=2.402,P=0.301;χ2=2.465,P=0.116);治疗有效和无效组的基因型和等位基因分布频率的差异无显著性(χ2=1.995,P=0.369;χ2=1.939,P=0.164);各基因型亚组的年龄、发病年龄及其病程差异均无显著性(P均大于0.05);但基因亚组A1/A1的治疗前PANSS总分(χ2=4.076,P=0.018)和阴性症状分(χ2=3.946,P=0.021)以及治疗结束PANSS总分减分率(χ2=4.036,P=0.019)和阴性症状减分率(χ2=3.876,P=0.022)均显著高于A1/A2及A2/A2基因型.结论(1)首发精神分裂症患者不同临床亚型5-HT2A受体基因T102C基因型和等位基因频率无显著差异.(2)利培酮高剂量组和低剂量组5-HT2A受体基因T102C基因型和等位基因分布频率没有显著性差异.(3)治疗有效组与无效组之间5-HT2A受体基因T102C基因型和等位基因分布频率也无显著性差异.(4)5-HT2A受体T102C Ai/A1基因亚型可能影响中国首发精神分裂症患者对利培酮的治疗效应.     

A functional single nucleotide polymorphism (V158M) in the COMT gene is associated with aggressive personality traits.

BACKGROUND: Suicidal behavior is often correlated with other-directed aggression, which is partially mediated by catecholaminergic neurotransmission. Catechol-O-methyltransferase (COMT) is an enzyme involved in catecholamine inactivation. In this study, we examined the influence of a functional COMT (V158M) polymorphism on suicidal behavior and anger-related traits. METHODS: This polymorphism was examined in 149 German suicide attempters and 328 German control subjects. Both groups were administered self-report questionnaires for anger-related traits. RESULTS: There was no overall difference in allele/genotype frequency between patients and control subjects; however, the low-activity L-allele and genotype frequencies were higher among violent suicide attempters. For anger-related traits, a multivariate effect of the COMT genotype was observed after controlling for age and educational level. LL-carriers expressed their anger more outwardly, whereas HH-carriers expressed it more inwardly and reported more state anger, as assessed by the self-report questionnaire. CONCLUSIONS: These findings support the hypothesis that the functional polymorphism in the COMT gene may modify the phenotype of suicide attempts and anger-related traits. This, however, being a novel finding, should warrant further investigation.