多巴胺转运体基因与精神分裂症

目的 探讨精神分裂症及其亚型与多巴胺转运体（ＤＡＴ１）基因间的关系。方法 采用Ａｍｐ－ＦＬＰ技术,对上海地区汉族人群中精神分裂症与ＤＡＴ１基因小卫星多态性进行遗传关联分析。结果 ⑴观察到ＤＡＴ１基因中５种等基因（３６０ｂｐ、４００ｂｐ、４４０ｂｐ、４８０ｂｐ、５２０ｂｐ）,最常见是４８０ｂｐ。⑵精神分裂症和健康对照组在ＤＡＴ１的等位基因、基因型的分布上无显著性差异（Ｚ值小于１．９６,Ｐ〉０．０５）     

α1—抗糜蛋白酶基因信号肽和微卫星多态性的关系及其对阿尔茨 …

目的 探讨中曙上海地区汉族人中α１抗糜蛋白酶（ＡＡＣＴ）基因中信号肽多态性和微卫星多态性的相互关系及其在阿尔茨海默病（ＡＤ）中的作用。方法 采用聚合酶链式反应－限制性片段长度多态性（ＰＣＲ－ＲＦＬＰ）方法及扩增片段长度多态性技术（Ａｍｐ－ＦＬＰ）,观察６３例ＡＤ患者和６８名健康老年人的ＡＡＣＴ基因信号肽多态性及微卫星多态性和早老素１（ＰＳＩ）基因、载脂蛋白Ｅ（ａｐｏＥ）基因多态的分布。结果 （１）     

早老素1基因多态性与迟发性阿尔茨海默病的遗传相关研究

目的 对中国广州汉族人群的早老素１（ＰＳ１）基因内含子８多态性与迟发性阿尔茨海默病（ＡＤ）进行关联分析。方法 应用聚合酶链反应和限制性片段长度多态性方法,检测１０４例迟发性ＡＤ患者（ＡＤ组）和１０６名正常老年人（对照组）的ＰＳ１基因内含子８的多态性,并对ＡＤ与ＰＳ１基因各等位基因及基因型进行了关联分析。结果 （１）ＡＤ患者组的ＰＳＩ等位基因１的频率（０．６０）高于对照组（０．４８）,等位基因２的频     

α1-抗糜蛋白酶基因、早老素1基因 与阿尔茨海默病的相关分析

目的探讨中国汉族人中α１抗糜蛋白酶（ＡＡＣＴ）基因、早老素１（ＰＳ１）基因多态性与阿尔茨海默病（Ａｌｚｈｅｉｍｅｒｓｄｉｓｅａｓｅ,ＡＤ）的相关情况。方法应用ＰＣＲＲＦＬＰ方法,在１２３例患者和１４０例正常人中观察ＡＡＣＴ信号肽和ＰＳ１基因多态性的分布,进行关联分析。结果１ＡＤ患者与ＰＳ１基因等位基因１正关联,与等位基因２和基因型２／２负关联,但与１／１基因型无关;２ＡＡＣＴ信号肽基因多态性与ＡＤ无关联;３在三种ＰＳ１基因型中,ＡＡＣＴ信号肽基因多态性与ＡＤ均无关;４在ＡＡＣＴ基因ＡＡ、ＴＴ基因型中,ＰＳ１基因多态性与ＡＤ负关联,而ＴＡ型中ＰＳ１基因与ＡＤ无显著相关。结论中国人群中,ＡＤ与ＰＳ１基因２／２型负关联,而与ＡＡＣＴ信号肽基因多态性无关;ＡＡＣＴ信号肽和ＰＳ１基因多态性之间也无明显的相互影响。     

第10号染色体缺失的磷酸酶张力蛋白同源物基因多态性与脑膜瘤易感性关联研究

目的 研究中国人群中第10号染色体缺失的磷酸酶张力蛋白同源物基因（PTEN）单核苷酸多态性与脑膜瘤发病风险的关系。方法 选取2017年10月—2018年1月在北京天坛医院神经外科手术治疗的200例脑膜瘤患者为研究对象,应用SNaPshot基因分型技术对PTEN基因多态位点rs2735343、rs701848和rs1234214检测,分析PTEN基因多态性与脑膜瘤的易感性。结果 PTEN基因多态位点rs2735343、rs701848和rs1234214基因频率在脑膜瘤组和对照组基因型和等位基因频率分布无差异（P＞0.05）。单体型分析结果显示CTC单体型频率在脑膜瘤组和对照组之间差异有统计学意义（P＜0.05）,CTC单体型携带者发生脑膜瘤的风险增加（OR=1.366,95%CI=1.034~1.805,P=0.028）。结论 PTEN基因多态性可能与脑膜瘤发病无关联,但PTEN基因rs2735343、rs701848和rs1234214构成的CTC单体型可能是中国人群脑膜瘤发病的危险因素。     

中国蒙,汉族酒依赖与醇脱氢酶和醛脱氢酶基因多态性的相关研究

为探讨醇脱氢酶（ＡＤＨ）基因和醛脱氢酶（ＡＬＤＨ）基因多态性与酒依赖患病的相互关系，用耳血干血痕聚合酶链反应、等位基因特异性寡核苷酸探针方法，检测乙醇代谢酶ＡＤＨ和ＡＬＤＨ基因型在我国蒙、汉民族酒依赖与非酒依赖者中分布频率。结果显示在酒依赖组（汉族５２例，蒙族３１例）与正常对照组（汉族４８例，蒙族３５例）之间：汉族的ＡＬＤＨ２基因型频率与等位基因频率的分布差异有非常显著性（Ｐ＜０．０１），而蒙族则表示为ＡＤＨ２基因型频率与等位基因频率的分布差异有非常显著性（Ｐ＜０．０１）。这提示汉族酒依赖的发病与ＡＬＤＨ２基因有关，蒙族则与ＡＤＨ２基因有关。     

双体型-同源染色体中配对的单体型对–在基因-疾病中的关联分析中的应用(英文)

等位基因,基因型和单体型(等位基因组合)已被广泛应用于基因-疾病的关联研究。最近,使用双体型(同源染色体单体型对)的关联研究已经越来越普遍。本文综述了四种关联分析类型的基本原理,并探讨了为什么以双体型为基础的关联分析比其他类型的关联分析更高效。单体型关联分析比基于等位基因的关联分析更高效,以双体型为基础的关联分析比基于基因型的关联分析更高效。在标记之间没有交互作用并且符合Hardy-Weinberg平衡(HWE)标准的情况下,以等位基因和单体型为基础的关联分析样本量较大、自由度较小,使它们分别比基因型和双体型为基础的关联分析更高效。然而,在某些情况下以双体型为基础的关联分析比单体型关联分析更高效。     

5-羟色胺2A受体基因多态性与阿尔茨海默病的关联分析

目的 探讨中国汉族人群中５－羟色胺（５－ＨＴ）２Ａ（５－ＨＴ２Ａ）受体基因多态性与阿尔茨海默病（ＡＤ）的相互关系,方法 应用聚合酶链式反应（ＰＣＲ）－限制片段长度多态性（ＲＦＬＰ）方法,在８２例ＡＤ患者和９７名正常人中观察了５－ＨＴ２Ａ受体基因和载脂蛋白Ｅ（ＡｐｏＥ）基因多态性的分布,结果 （１）５－ＨＴ２Ａ受体基因多态性与ＡＤ是不存在任何关联（Ｐ〉０．０５）;（２）在进行ＡｐｏＥ基因分型后,Ａｐ     

亨廷顿氏病发病及基因诊断

亨廷顿氏病（Ｈｕｎｔｉｎｇｔｏｎｓ，ｄｉｓｅａｓｅ，ＨＤ）是神经系统一种严重的常染色体显性遗传病［１］。该病的遗传学基因是在ＩＴ１５基因的开放阅读框架的５’端有一个多态的（ＣＡＧ）ｎ三核苷酸重复序列异常扩增，在正常人群中其拷贝数为１１～３４，而ＨＤ...     

载脂蛋白E基因-219G/T多态与阿尔茨海默病的相关研究

目的　探讨上海地区汉族人群中载脂蛋白E基因 (ApoE)启动子区 2 1 9G/T多态与阿尔茨海默病(Alzheimer’sdisease,AD)发病风险的关系。方法　采用聚合酶链式反应 (PCR)和限制性片段长度多态 (RELP)方法 ,于 1 0 4例AD患者和 1 1 1例正常人中检测 2 1 9G/T多态各基因型及基因频率的分布。按比值比 (OR)作疾病关联分析。结果　①AD患者与正常对照人群之间不存在 2 1 9G/T多态各等位基因和基因型频率分布的差异 (P值均大于0 0 5) ;②按ApoEε4基因分层后 ,无论是ε4型人群还是非ε4型人群中都不存在AD患者与正常对照人群间的多态分布的差异 (P值均大于 0 0 5) ;③ 2 1 9G/T多态各基因型的分布不影响AD与ApoEε4等位基因的关联。结论　上海地区汉族人群中 ,ApoE基因启动子区 2 1 9G/T多态与AD无关     

A preliminary report of the dopamine receptor D4 and the dopamine transporter 1 gene polymorphism and its association with attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent childhood-onset psychiatric syndromes affecting 5%–10% of school-age children worldwide. Distortions in the catecholaminergic system seem to be responsible for this condition. Within this system there are several candidate genes, the dopamine receptor D₄ (DRD4) and the dopamine transporter 1 (DAT1), with common polymorphism which might be associated with ADHD. We performed a family based association study with 36 trios and 19 parent proband pairs. All diagnoses were confirmed by the “Hypescheme” diagnostic computer program. In this study we did not observe an association of ADHD with DRD4 and DAT1 polymorphism neither by the haplotype relative risk (HRR) method nor by the transmission disequilibrium test (TdT) method. The odds ratio for the DRD4 7-allele was 1.01 and 0.94 for both statistical tests, respectively, and the respective odds ratio for the DAT1 6-allele were 0.91 and 0.88.     

A common haplotype of the dopamine transporter gene associated with attention-deficit/hyperactivity disorder and interacting with maternal use of alcohol during pregnancy

CONTEXT: Attention-deficit/hyperactivity disorder (ADHD) is a common heritable childhood behavioral disorder. Identifying risk factors for ADHD may lead to improved intervention and prevention. The dopamine transporter gene (DAT1) is associated with ADHD in several studies, with an average 1.2 odds ratio and evidence of heterogeneity across data sets. OBJECTIVE: To investigate sources of heterogeneity by refining the DAT1 association using additional markers and investigating gene-environment interaction between DAT1 and maternal use of alcohol and tobacco during pregnancy. DESIGN: Prospective study. SETTING AND PATIENTS: Children with ADHD from child behavior clinics in the southeast of England and in the Taipei area of Taiwan. INTERVENTIONS: Within-family tests of association using 2 repeat polymorphisms in the 3' untranslated region and intron 8 plus additional markers in the English sample. MAIN OUTCOME MEASURES: Transmission ratios of risk alleles from heterozygote parents to affected offspring and comparison of the transmission ratios in high- and low-exposure groups for the environmental variables. RESULTS: A novel association was identified between ADHD, the intron 8 polymorphism, and a specific risk haplotype in both English and Taiwanese samples. The risk haplotype showed significant interactions with maternal use of alcohol during pregnancy. CONCLUSIONS: The identification of a common haplotype in 2 independent populations is an important step toward identifying functionally significant regions of DAT1. Interaction between DAT1 genotypes and maternal use of alcohol during pregnancy suggests that DAT1 moderates the environmental risk and has implications for the prevention of ADHD. Further studies are required to delineate the precise causal risk factor involved in this interaction.     

多巴胺转运体基因与迟发性运动障碍的关联性

目的：探讨多巴胺转运体(DAT1)基因小卫星多态与迟发性运动障碍(TD)的关联性。方法：采用Amp—FLP技术，对99例精神分裂症伴TD患者和120名正常人的DAT1基因多态性进行检测，比较各组间等位基因和基因型频率分布的差异。结果：共观察到5种等位基因：320bp、360bp、440bp、480bp和520bp。经吻合度检验，TD组和正常对照组DAT1基因各基因型的分布均符合Hardy-Weinberg平衡法则。与正常对照组相比较，TD组中仅360bp等位基因频率显著减少(P＜0．05)。经关联性分析，DAT1基因该多态与TD不相关联。在TD组中，基因型频数及等位基因频数与病程、家族史、药物、剂量和异常不自主运动评定量表(AIMS)评分无显著性意义(P＞0．05)：结论：DAT1基因该位点多态可能与TD的发生无关。     

精神分裂症和亚甲基四氢叶酸还原酶基因的核心家系研究

目的探讨亚甲基四氢叶酸还原酶(MTHFR)基因与中国西北地区汉族精神分裂症的关系。方法应用聚合酶链反应-限制性片段长度多态性方法(PCR-RFLP),检测106个精神分裂症核心家系MTHFR基因的C677T和A1298C多态性,采用单倍体相对风险(HRR)和传递不平衡检验(TDT)分析MTHFR基因与精神分裂症的关系。结果①患者组与父母组MTHFR基因C677T和A1298C多态性基因型频率分布差异无统计学意义(x2=0.369,P>0.05;x2=1.214,P>0.05)。②HRR分析显示C677T、A1298C两位点等位基因在病例组和父母对照组的频数分布差异无统计学意义(x2=0.236,P>0.05;x2=3.327,P>0.05)。③TDT检验未发现C677T和A1298C两位点在精神分裂症中存在传递不平衡(x2=0.243,P>0.05;x2=2.123,P>0.05)。结论未发现MTHFR基因C677T和A1298C多态性与精神分裂症存在关联。     

Psychotherapy as a treatment modality for psychiatric disorders: Perceptions of general public of Karachi, Pakistan

Background

Attention deficit hyperactivity disorder (ADHD) is a complex neurobehavioral disorder. The dopamine transporter gene (DAT1/SLC6A3) has been considered a good candidate for ADHD. Most association studies with ADHD have investigated the 40-base-pair variable number of tandem repeat (VNTR) polymorphism in the 3'-untranslated region of DAT1. Only few studies have reported association between promoter polymorphisms of the gene and ADHD.

Methods

To investigate the association between the polymorphisms -67A/T (rs2975226) and -839C/T (rs2652511) in promoter region of DAT1 in ADHD, two samples of ADHD patients from the UK (n = 197) and Taiwan (n = 212) were genotyped, and analysed using within-family transmission disequilibrium test (TDT).

Results

A significant association was found between the T allele of promoter polymorphism -67A/T and ADHD in the Taiwanese population (P = 0.001). There was also evidence of preferential transmission of the T allele of -67A/T polymorphism in combined samples from the UK and Taiwan (P = 0.003). No association was detected between the -839C/T polymorphism and ADHD in either of the two populations.

Conclusion

The finding suggests that genetic variation in the promoter region of DAT1 may be a risk factor in the development of ADHD.     

The dopamine transporter gene is associated with attention deficit hyperactivity disorder in a Taiwanese sample

Genetic variation of the dopamine transporter gene (DAT1) is of particular interest in the study of attention-deficit hyperactivity disorder (ADHD), since stimulant drugs interact directly with the transporter protein. Association between ADHD and the 10-repeat allele of a 40-bp VNTR polymorphism that lies within the 3'-UTR of DAT1 was first reported in 1995, a finding that has been replicated in at least six independent samples from Caucasian populations. We analysed the DAT1 polymorphism in a sample of 110 Taiwanese probands with a DSM-IV diagnosis of ADHD and found evidence of increased transmission of the 10-repeat allele using TRANSMIT (chi(2)=10.8, 1 d.f., p=0.001, OR=2.9, 95% CI 1.4-6.3). These data give rise to a similar odds ratio to that observed in Caucasian poplulations despite a far higher frequency of the risk allele in this Taiwanese population; 82.3% in the un-transmitted parental alleles and 94.5% in the ADHD probands. These data support the role of DAT1 in ADHD susceptibility among Asian populations.     

Association between the dopamine transporter gene and the inattentive subtype of attention deficit hyperactivity disorder in Taiwan

Attention deficit hyperactivity disorder (ADHD) is a common heritable childhood psychiatric disorder. Since methylphenidate, one of the main drugs used to treat ADHD, targets the dopamine transporter, this study examined the linkage disequilibrium (LD) structure of the dopamine transporter gene (DAT1) and investigated whether the DAT1 gene was associated with ADHD. This Chinese family-based association sample consisted of 273 DSM-IV diagnosed ADHD probands and their family members (n = 906). We screened 15 polymorphisms across the DAT1 gene, including 14 single nucleotide polymorphism (SNP) markers and the variable number of tandem repeat (VNTR) polymorphism in 3′-untranslated region (3′UTR). Calculations of pairwise LD revealed three main haplotype blocks (HBs): HB1 (intron 2 through intron 6), HB2 (intron 8 through intron 11), and HB3 (3′UTR). Family-Based Association Tests showed that no allele was significantly more transmitted than expected to the ADHD children for these 15 markers. Haplotype-Based Association Tests showed that a haplotype rs27048 (C)/rs429699 (T) was significantly associated with the inattentive subtype (P = 0.008). In quantitative analyses, this haplotype also demonstrated significant association with the inattention severity (P = 0.012). Our finding of the haplotype rs27048 (C)/rs429699 (T) as a novel genetic marker in the inattentive ADHD subtype suggests that variation in the DAT1 gene may primarily affect the inattentive subtype of ADHD.     

Interacting effects of the dopamine transporter gene and psychosocial adversity on attention-deficit/hyperactivity disorder symptoms among 15-year-olds from a high-risk community sample

CONTEXT: Recent evidence suggests that gene x environment interactions could explain the inconsistent findings of association studies relating the dopamine transporter (DAT1) gene with attention-deficit/hyperactivity disorder (ADHD). OBJECTIVE: To examine whether psychosocial adversity moderated the effect of genetic variation in DAT1 on ADHD symptoms in adolescents from a high-risk community sample. DESIGN: Prospective cohort study. SETTING: Data were taken from the Mannheim Study of Children at Risk, an ongoing longitudinal study of the long-term outcomes of early risk factors followed up from birth on. PARTICIPANTS: Three hundred five adolescents (146 boys, 159 girls) participated in a follow-up assessment at age 15 years. MAIN OUTCOME MEASURES: Measures of ADHD symptoms according to DSM-IV were obtained using standardized structural interviews with adolescents and their parents. Psychosocial adversity was determined according to an "enriched" family adversity index as proposed by Rutter and Quinton. DNA was genotyped for the common DAT1 40-base pair (bp) variable number of tandem repeats (VNTR) polymorphism in the 3' untranslated region; 3 previously described single nucleotide polymorphisms in exon 15, intron 9, and exon 9; and a novel 30-bp VNTR polymorphism in intron 8. RESULTS: Adolescents homozygous for the 10-repeat allele of the 40-bp VNTR polymorphism who grew up in greater psychosocial adversity exhibited significantly more inattention and hyperactivity-impulsivity than adolescents with other genotypes or who lived in less adverse family conditions (significant interaction, P = .013-.017). This gene x environment interaction was also observed in individuals homozygous for the 6-repeat allele of the 30-bp VNTR polymorphism and the haplotype comprising both markers. CONCLUSIONS: These findings provide initial evidence that environmental risks as described by the Rutter Family Adversity Index moderate the impact of the DAT1 gene on ADHD symptoms, suggesting a DAT1 effect only in those individuals exposed to psychosocial adversity.     

Further evidence for the association between a polymorphism in the promoter region of SLC6A3/DAT1 and ADHD: findings from a sample of adults

The dopamine transporter (SLC6A3/DAT1) plays a key role in the regulation of dopaminergic neurotransmission and is the major site of action for methylphenidate, a first-line medication for attention deficit hyperactivity disorder (ADHD). Most genetic association studies with ADHD have investigated a 40-bp variable number of tandem repeats (VNTR) polymorphism in the 3′-untranslated region (UTR) of the DAT1, but these investigations have reported heterogeneous findings. The few studies focused on the 5′ region have reported promising results. Despite rs2652511 not being included, nor having any proxy SNP available in GWAS, the few candidate gene studies that analyzed it suggested an association with ADHD and schizophrenia. Here, we analyzed the ?839 C/T (rs2652511) promoter variant and the 3′-UTR and intron 8 (Int8) VNTR polymorphisms in 522 adults with ADHD and 628 blood donor controls. The diagnostic procedures followed the DSM-IV criteria. A significant association was detected (P = 0.002) between the rs2652511 C-allele with ADHD. In addition, the 6-repeat allele of Int8 VNTR was associated with higher inattention scores (P = 0.034). The haplotype analysis including DAT1 3′-UTR and Int8 VNTR polymorphisms did not reveal associations with ADHD susceptibility or severity dimensions. These findings extend to adult samples previous findings from children samples on the role of the rs2652511 polymorphism in the promoter region of DAT1 as a risk factor for ADHD susceptibility.     

低密度脂蛋白受体相关蛋白1基因多态性与中国人阿尔茨海默病发病风险的meta分析

目的 探讨低密度脂蛋白受体相关蛋白1（LRP-1）基因C766T位点多态与中国人阿尔茨海默病（AD）发病风险的关系。方法 应用LRP-1、low density lipoprotein receptor related protein 1 gene、阿尔茨海默病等关键词,检索中国期刊全文数据库（CJFD）、Medline、Cochrane图书馆与中国生物医学文献数据库（CBMdisc）4个数据库,对1997年1月至2019年6月公开发表的关于中国人阿尔茨海默病LRP-1基因多态性的病例对照研究进行meta分析。结果 共纳入16项病例对照研究。综合数据分析,CC基因型及C等位基因与中国人AD发病相关,均P<0.05,差异有统计学意义;中国人携带CC基因型发生AD的风险是携带CT/TT基因型的1.477倍,携带C等位基因发生AD的风险是携带T等位基因的1.669倍。CC基因型及C等位基因与汉族人AD发病亦相关,均P<0.05,差异有统计学意义;汉族人携带CC基因型发生AD的风险是携带CT/TT基因型的1.711倍,携带C等位基因发生AD的风险是携带T等位基因的2.005倍。结论 LRP-1基因C766T位点多态性与中国人,尤其是汉族人AD发病风险相关,携带CC基因型和C等位基因的个体有更大风险发生AD。