褪黑素合成酶ASMT基因启动子和第一外显区单核苷酸多态性与儿童孤独症的关联研究

目的探讨参与褪黑素合成的乙酰血清素甲基转移酶(acetylserotonin methyltransferase,ASMT)基因启动子和第1外显子区遗传多态性位点与儿童孤独症是否关联。方法对390例儿童孤独症患者和420例正常对照者的ASMT基因启动子和第1外显子区域进行测序。比较该区域5个单核苷酸多态性(single nucl-eotide polymorphisms,SNPs)位点的等位基因频率、基因型频率和单体型频率在患者组与对照组之间的差异。结果患者组和对照组之间,5个SNPs(rs4446909、rs5989681、rs56690322、rs6644635、rs17149149)等位基因和基因型频率的差异均无统计学意义(P>0.05)。3个SNPs位点rs4446909、rs5989681和rs6644635之间存在连锁不平衡(linkage disequilibrium,LD)(D’值为0.85-0.98)。但此3个SNPs构成的单体型频率在两组间的差异无统计学意义(P>0.05)。结论本研究未发现ASMT基因启动子和第1外显子区域的遗传多态性位点与儿童孤独症关联,提示这些位点可能未参与中国汉族人群孤独症的致病。     

谷氨酸受体6基因多态与孤独症的关联分析

目的 在中国上海地区汉族孤独症家系中探讨谷氨酸受体6（GluR6或GRIK2）基因多态与孤独症是否关联。方法 采用PCR—RFLP法对入组的38个孤独症核心家系成员的GRIK2基因的两个单核苷酸多态性（rs6922753和rs2227283）分型,并进行传递不平衡检验。结果 rs6922753多态的C和T等位基因未发现显著性的偏移传递方式,rs2227283多态在母系传递中出现显著性的偏移,A等位基因较G等位基因传递明显增加。结论 GRIK2基因与孤独症存在传递的连锁不平衡,可能为孤独症的易感基因。     

5-羟色胺转运体基因多态性与儿童孤独症核心家系的关联研究

目的 探讨中国汉族人群5-羟色胺转运体基因多态性(5-HTTLPR)与儿童孤独症的关系。方法 应用聚合酶链式反应技术(PER),测定了82个儿童孤独症核心家系患儿及其父母的基因型和等位基因。结果 传递不平衡检验(TDT)显示等位基因传递无统计学意义(X2=0.014,P>0.05)。结论 5-HTTLPR与儿童孤独症没有关联,5一羟色胺转运体基因可能在儿童孤独症发病中不起主要作用。     

CLTCL1 基因 rs1061325 位点多态性与中国 汉族精神分裂症的关联分析

目的 探讨中国汉族人群网格蛋白重链 1（CLTCL1）基因 rs1061325 多态性与精神分裂症 的相关性。方法 选取 2007— 2008 年在上海交通大学医学院附属精神卫生中心门诊或住院的 662 例 精神分裂症患者作为病例组，选取同期的 414 名健康志愿者作为对照组。采用 TaqMan 探针基因分型技 术对两组的 CLTCL1 基因 rs1061325 位点进行分型，采用阳性与阴性症状量表（PANSS）对病例组进行精 神症状严重程度评定，并分析 PANSS 评分与不同基因型的相关性。结果 病例组与对照组的 rs1061325 等位基因和基因型频率分布比较，差异无统计学意义（χ2 =0.25、0.28，P=0.62、0.87）；在共显性、显性、隐 性、超显性、加性遗传模式下基因型分布差异也无统计学意义（P＞ 0.05），rs1061325 基因型多态性对精 神分裂症患者的发病年龄［（24.15±6.71）岁］、病程［（31.23±9.49）年］和 BMI［（26.46±5.28）kg/m2 ］也均 无明显影响（F=1.15、0.33、0.75，P=0.32、0.72、0.48），rs1061325 基因型多态性与 PANSS 阳性症状分、阴 性症状分、一般精神病理分及 PANSS 总分无相关性（F=1.26、0.37、0.34、0.49，P=0.29、0.69、0.72、0.62）。 结论 在中国汉族人群中，CLTCL1 基因 rs1061325 位点与精神分裂症无关联。     

丝裂酶原活化蛋白激酶1基因多态性与中国汉族阿尔茨海默病的关联研究

目的:研究探讨丝裂酶原活化蛋白激酶1(MAPK1)基因在中国汉族阿尔茨海默病(AD)发生过程中的作用。方法:根据《美国精神障碍诊断和统计手册》(DSM-IV)和美国国立神经病、语言功能紊乱和脑卒中研究所及AD和相关疾病协会临床诊断标准(NINCDS-ADRDA),收集中国东部和西南部人群AD患者715例和健康对照者760人。选取MAPK1基因3个标签多态性位点rs2276006、rs1063311和rs2006893。采用SNa Pshot SNP分型技术对这3个SNP位点进行分析。结果:中国东部和西南部人群AD组与对照组间MAPK1基因各位点基因多态性及等位基因分布频率差异无统计学意义(P0.05);东部及西南部人群合并后AD组与对照组间MAPK1基因各位点基因多态性及等位基因分布频率差异无统计学意义(P0.05),连锁不平衡检验显示各SNP位点之间存在强连锁(D'0.95),单体型分析结果显示病例组与对照组间单体型估计频率差异无统计学意义(P0.05)。结论:MAPK1基因可能不是中国汉族AD的主要致病基因。     

APOE基因多态性与抑郁症和痴呆的关联分析

目的：探索基因与抑郁症和痴呆的关联。方法：对42例单相抑郁症,39例双相抑郁症,40例痴呆和100例健康对照者进行载脂蛋白E（appolipoprotein,APOE)基因分型,计算基因频率,并对抑郁症、痴呆与APOE基因多态性进行关联分析。结果：抑郁症和痴呆的APOEε2等位基因频率比对照组低,单相抑郁症和痴呆的APOEε4等位基因频率高于对照组,且APOEε4等位基因与痴呆密切关联。结论：APOEε2基因可能是抑郁的保护因子,痴呆与单相抑郁症可能分享共同的发病因子。     

APOE基因多态性与单相抑郁症无关联

目的 探讨APOE基因与单相抑郁症之间的关系。方法 以73例单相抑郁症患者为研究对象,80例健康人为对照组。用聚合酶链反应（PCR）扩增技术及限制性片段长度多态性（RFLPs)技术测定研究对象的APOE基因多态性。结果 发现单相抑郁症与APOE基因的多态性之间无关联。结论 APOE基因对上海汉族人群中单相抑郁症的病因可能不起重要作用。     

色氨酸羟化酶基因多态性与精神分裂症的关联研究

目的探讨中国汉族人群色氨酸羟化酶(TPH)基因A218C多态性与精神分裂症的关系。方法选取符合美国精神障碍诊断与统计手册第4版(DSM-IV)精神分裂症诊断标准的患者212例和正常对照168名,应用聚合酶链式反应(PCR)扩增及限制性片段长度多态性(RFLP)技术检测TPH基因A218C多态性,比较两组基因型和等位基因频率。结果TPH基因的A218C多态性基因型和等位基因频数在患者组与对照组间的分布差异无统计学意义(P>0.05)。②女性患者等位基因A频率显著高于女性对照组(χ2=4.905,P=0.027,OR=1.637,95%CI:1.057~2.536)。③早发型与晚发型分裂症间基因型和等位基因频率的差异无统计学意义(P>0.05)。④患者组家族史阴性和阳性亚组间的A218C多态性的基因型和等位基因频率的差异无统计学意义(P>0.05)。结论TPH基因A218C多态性等位基因A可能是女性精神分裂症的危险因子。     

儿童孤独症候选基因研究进展

儿童孤独症或称自闭症,是一种广泛的心理发育障碍,它影响到儿童的感知、语言、情感和社会交往等多种功能。越来越多的证据表明遗传因素在儿童孤独症病因中起着一定的作用,本文将对儿童孤独症的分子遗传学研究现状和进展作一综述。     

Pin 1基因单核苷酸多态性与阿尔茨海默病的关联研究

目的 探讨中国汉族人群中Pin 1基因单核苷酸多态性与阿尔茨海默病的关系.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,检测107例阿尔茨海默病(AD)患者及110名正常对照的Pin 1基因rs2233678位点(-842)基因多态性,进行两组的比较并分析各基因型与年龄、性别、疾病严重程度的关系.结果 AD组和对照组基因型频率及等位基因频率差异均无统计学意义(P=0.098,P=0.10),进一步将样本按年龄和性别分层也未发现两组间的差异有统计学意义(P>O.05).不同基因型组间的简易智能状态检查(MMSE)评分的差异无统计学意义(P>O.05),提示其与AD疾病严重程度不相关.结论 未发现中国汉族人群中Pin 1基因rs2233678位点多态性与AD关联.     

The association between two single nucleotide polymorphisms within the insulin-degrading enzyme gene and Alzheimer's disease in a Chinese Han population

Several previous studies on the relationship between the insulin-degrading enzyme (IDE) gene and Alzheimer's disease (AD) have connected certain genetic variants to late-onset AD, in the absence of the apolipoprotein E (APOE)ε4 allele. However, the conclusions of these studies remain controversial. We investigated the association between two polymorphisms of IDE with AD in the Chinese population and found that the T/A genotype of rs4646958 had an important role in AD (adjusted p=0.007, odds ratio [OR]=2.796, 95% confidence interval [CI]=1.330-5.878), under the co-dominant genetic model. The T/C genotype of rs1887922 was also significantly associated with AD compared to the T/T genotype (adjusted p=0.003, OR=2.644, 95% CI=1.407-4.970). The C allele of rs1887922 conferred a higher risk of AD under the dominant genetics model (adjusted p=0.001, OR=2.719, 95% CI=1.472-5.022). Compared with the two other variant genotypes, the T/T genotype showed a protective effect in both polymorphisms (adjusted p=0.007, OR=0. 358, 95% CI=0.170-0.752 for rs4646958; adjusted p=0.001, OR=0. 368, 95% CI=0.199-0.679 in rs1887922). In the context of APOEε4-negative status, both variants were significantly associated with AD in some genetic models.     

代谢型谷氨酸受体3基因多态性与酒依赖的关联研究

目的探讨中国北方汉族人群代谢型谷氨酸受体3(GRM3)基因多态性与酒依赖的相关性。方法采用聚合酶链反应(Polymerase Chain Reaction,PCR)和连接酶检测反应(Ligase Detection Reaction,LDR)方法,检测100例酒依赖患者和100例正常对照的GRM3基因上3个位点rs1468412、rs917071和rs1989796的基因多态性。结果酒依赖组和对照组之间GRM3基因rs1468412、rs917071以及rs1989796位点的等位基因频率和基因型分布的差异均无统计学意义(P>0.05),但酒依赖组中rs1468412、rs917071和rs19897963个位点所构建的单倍型TTT的频率明显高于对照组(6%vs.1%,OR=5.17,P<0.05),TTT基因型携带者患酒依赖的可能性较高。结论在本样本中,中国北方汉族人群GRM3基因rs1468412、rs917071和rs1989796位点的多态性单独存在时与酒依赖无关联,而由此3个位点所构建的单倍型TTT可能为酒依赖的易感危险因素。     

ALOX5AP基因启动子区单核苷酸多态性与中国北方汉族人群缺血性卒中的关系

目的探讨ALOX5AP基因启动子区单核苷酸多态性与中国北方汉族人群缺血性脑血管病的相关关系。方法本研究共人选北方汉族脑梗死患者220例，同期年龄与性别匹配的对照组191名。采用聚合酶链反应目的基因扩增和基因直接测序的方法鉴别基因型和单核苷酸多态性分析。病例组和对照组基因型分布差异采用关联分析的方法进行检测。经多元Logistic回归方法校正经典血管病危险因素后，分析基因多态性与缺血性卒中的相关关系。结果发现3个ALOX5AP启动子区未报道的单核苷酸多态性位点，由这3个位点组成的单体型与缺血性脑血管病的发生明确相关，其中Hap Ⅰ是一种保护性单体型，可以减少缺血性脑血管病发生（OR 0．54，95％CI 0．408～0．715）；而HapⅡ（OR 2．91，95％CI 1．351～6．239）和Hap Ⅲ （OR 18．82，95％CI 2．562～138．38）则作为一种危险因素，增加缺血性脑血管病发生的风险。另外，-499和-290位点单核苷酸多态性与全脑动脉粥样硬化密切相关。结论与炎症介质白三烯代谢密切相关的ALOX5AP基因启动子区单核苷酸多态性与中国北方汉族人群脑梗死的发生有密切关系。     

No association between thrombosis and factor V gene polymorphisms in Chinese Han population

Activated protein C resistance (APCR) is the most common hereditary condition of thrombosis in Western countries. And it is significantly linked to a single nucleotide polymorphisms (SNPs) in the coagulation factor V gene that results in the mutations at R506, R306 and HR2 alleles. To determine the prevalence of APCR and its association with the factor V gene SNPs in Chinese Han thrombotic patients, we investigated a total of 346 Chinese thrombotic patients and 140 normal controls for APCR using the APTT-based assays, according to manufacturer's instructions, APC ratio 相似文献   

Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population.

BACKGROUND: Previous research has suggested that the social impairments exhibited by individuals with autism are associated with changes in plasma oxytocin (OT) levels. The physiologic effects of oxytocin are mediated through its specific receptors (OTRs), and numerous studies have implicated OTRs in the regulation of social cognition and behavior. Animal models and linkage data from genome screens indicate that the oxytocin receptor gene (OXTR) is an excellent candidate for research concerning psychiatric disorders, particularly those involving social impairments, such as autism. METHODS: We genotyped four single nucleotide polymorphisms (SNPs) located within the OXTR gene of 195 Chinese Han autism trios, using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The family-based association test (FBAT) revealed a significant genetic association between autism and two of the SNPs tested (rs2254298 A: Z = 2.287, p = .0222; rs53576 A: Z = 2.573, p = .0101). When haplotypes were constructed with two, three, and four markers, the haplotype-specific FBAT revealed that a number of haplotypes, particularly those involving rs53576, were significantly associated with autism. Furthermore, haplotypes constructed with all markers showed a significant excess transmission for the specific and global haplotype analyses (p = .0020 and .0289, respectively). CONCLUSIONS: These data suggest an involvement of OXTR in the susceptibility to autism, and replication is important.     

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.     

A study of single nucleotide polymorphisms in CD157, AIM2 and JARID2 genes in Han Chinese children with autism spectrum disorder

Purpose: Autism spectrum disorder (ASD) is a group of developmental brain disorders caused by genetic and environmental factors. The objective of this study was to investigate whether single nucleotide polymorphisms (SNPs) in genes related to immune function were associated with ASD in Chinese Han children.

Materials and methods: A total of 201 children with ASD and 200 age- and gender-matched healthy controls were recruited from September 2012 to June 2106. A TaqMan probe-based approach was used to genotype SNPs corresponding to rs28532698 and rs4301112 in CD157, rs855867 in AIM2, and rs2237126 in JARID2. Case-control and case-only studies were performed to determine the contribution of SNPs to the predisposition of disease and its severity, respectively.

Results: Our results revealed that the genotypes and allele frequencies of these SNPs were not significantly associated with childhood ASD and its severity in this population.

Conclusions: Results of our study suggest that these SNPs are not predictors of childhood ASD in the Chinese Han population. The discrepant results suggest the predictor roles of SNPs have to be determined in different ethnic populations due to genetic heterogeneity of ASD.     

Association of Parkinson's disease with six single nucleotide polymorphisms located in four PARK genes in the northern Han Chinese population

Parkinson's disease (PD) has widely been reported to be associated with mutations in the PARK genes. To investigate potential genetic risk factors for PD in a northern Han Chinese population, six single nucleotide polymorphisms (SNP) (R366W, V380L, P196S, R1628P, G2385R and R461W) located in four PARK genes were multiplex-amplified in two independent polymerase chain reaction (PCR) systems. Restriction fragment length polymorphisms (RFLP) were subsequently genotyped with Hae III endonuclease digestion in samples from 202 patients with PD and 212 control participants. High-throughput, multiplexed PCR-RFLP assays were able to accurately identify all six SNP. The genotypic frequency of G2385R in PARK8 was significantly different between the patient and control groups; however, the remaining SNP were not associated with PD. No heterogeneity was observed in the R461W site, and only one P196S site was found in the patient group. The polymorphic sites R366W and V380L and R1628P and G2385R were not in linkage disequilibrium. Carriers of 2385R presented at a higher Hoehn-Yahr stage compared to non-carriers. This study demonstrated an association of the G2385R allele with risk for PD in a northern Han Chinese population.     

No association of polymorphisms in the CDK5, NDEL1, and LIS1 with autism in Chinese Han population

Autism is a pervasive neurodevelopmental disorder. CDK5 (cyclin-dependent kinase 5) and its interacting molecules are involved in neurodevelopment. We performed a family-based association analysis between CDK5, NDEL1, and LIS1 polymorphisms and autism in a Chinese Han population. Our study did not detect a significant association. It indicated that common genetic variations in these genes might not play a role in the genetic predisposition to autism.