谷氨酸/多巴胺系统5个候选基因14个多态性与注意力缺陷多动障碍的关联

目的：注意力缺陷多动障碍(ADHD)是儿童常见行为障碍，病因不明。该文旨在探讨ADHD与5个基因14个多态位点的关系，以及与多位点联合效应的关系，寻找可增加患病风险的某些位点的特定组合。方法：对138名ADHD患者和119名正常对照进行以下遗传学分析：①用PCR-RFLP分析8个SNP位点；用PCR结合PAGE分析DRD4的48 bp VNTR；用基因扫描分析5个微卫星多态。②采用logistic回归法研究12个多态位点对ADHD的联合效应。结果：①ADHD组SNAP-25的T1065G多态性1065T/1065T基因型和1065T等位基因频率均明显高于对照组(均P<0.05)，DRD1 的A-48G多态性-48G/-48G频率明显低于对照组(P<0.05)。②发现了一个由2个基因3个SNP位点组成的特定基因型组合与ADHD有关联，其预测水平为77.5%。结论：SNAP-25的T1065G与ADHD可能有关联，1065T/1065T和1065T可能是其危险因素；DRD1的A-48G多态性与ADHD可能有关联，-48G/-48G可能是其保护因素；所发现的特定基因型组合支持“一些位点的特定组合效应增加了ADHD发病风险”的观点。［中国当代儿科杂志，2009，11（8）：617-622］

Association of 14 polymorphisms in the five candidate genes and attention deficit hyperactivity disorder

Objective Attention deficit hyperactivity disorder(ADHD)is one of the most common behavior disorders in childhood and adolescent.The etiology of ADHD is unknown.The aim of this study was to investigate the relationship between each of the 14 polymorphisms in the five candidate genes and ADHD,and between the combination of some polymorphisms in those genes and ADHD,in attempting to examine whether combinations of genotypes would confer a significant susceptibility to ADHD.Methods One hundred and thirty-nine children with ADHD and one hundred and nineteen normal children were enrolled.Eight single nucleotide polymorphisms(SNP)of three candidate genes were examined with PCR and RFLP techniques.48 bp VNTR in DRD4 gene was examined with PCR,nondenaturing polyacrylamide gel electrophoresis and silver staining.Five microsatellites(MS)of three candidate genes were examined with genotyping.The relationship between the combinations of 12 polymorphisms and ADHD was examined with logistic regression analysis.Results(1)The frequency of 1065T/1065T genotype and the 1065T allele were significantly higher in ADHD children than that in normal controls(P<0.05).The frequency of-48G/-48G genotype of the A-48G polymorphism of DRD1 gene was significantly lower in ADHD children than that in normal controls(P<0.05).(2)A specific combination of three polymorphisms in the two genes showing an association with ADHD gave a prediction level of 77.5%.Conclusions The T1065G polymorphism in the SNAP-25 may be associated with ADHD.The 1065T/1065T genotype and the 1065T allele may be a risk factor for ADHD.The A-48G polymorphism of DRDI may be associated with ADHD.The-48G/-48G genotype may be a protective factor for ADHD.The specific combination of three sites of SNP in SNAP-25 gene and DRDI gene is found and shows an association with ADHD in 12 polymorphisms of the five candidate genes on glutamatergic/dopaminergic pathway.