注意缺陷多动障碍与多巴胺转运体基因的关联分析

摘要

目的 分析多巴胺转运体基因3′端40bp可变数串联重复多态性与注意缺陷多动障碍之间的关系.方法 运用聚合酶连反应和可变数串联重复多态性分析技术对西安地区汉族人群中54例符合美国精神障碍诊断和统计手册第4版诊断标准的注意缺陷多动障碍儿童(n=54)及其父母(n=108)和正常对照组(n=66)进行多巴胺转运体基因3′端40bp可变数串联重复多态性检测,采用病例对照研究和核心家系关联分析(HRR和TDT)等统计方法进行注意缺陷多动障碍与多巴胺转运体基因多态性的关联分析.结果 所测人群中多巴胺转运体的40bp可变数串联重复多态性表现出7～11倍重复的5种等位基因,其中最常见的等位基因为10倍重复的480bp片段,占90.6%.共检出6种基因型,其中最常见的基因型为480bp/480bp,占82.1%.各基因型频率和等位基因频率在注意缺陷多动障碍组与对照组和核心家系中的分布均无显著性差异(均P>0.05).基因型为非480bp/480bp型在Conners-T教师问卷品行、多动、注意分散、多动指数和行为总分均高于基因型480bp/480bp,但无显著性差异(P>0.05).对54个注意缺陷多动障碍核心家系进行HRR和TDT关联分析,未显示注意缺陷多动障碍和多巴胺转运体基因存在关联.结论 在西安地区汉族人群中多巴胺转运体基因与注意缺陷多动障碍之间无显著性关联,多巴胺转运体基因多态性中的10倍重复等位基因可能不是注意缺陷多动障碍的遗传危险因素.%Objective To investigate correlation between polymorphism of 40bp variable number of tandem repeat(VNTR) that located in 3'untranslated region of DAT1 gene and ADHD. Methods Polymerase chain reaction (PCR) and VNTR polymorphism analysis technique were used to test polymorphism of 40bp VNTR that located in 3' untranslated region of the DAT1 gene of 54 ADHD children who were diagnosed according to DSM-Ⅳ criteria and 108 parents and 66 normal control children in Hah population from Xi'an city. Case-control study and family-based genetic association studies ( HRR and TDT analyses) were used to analyze correlation between DAT1 gene polymorphism and ADHD. Results ①In the population investigated, the repeat numbers of 40bp were 7 to 11 (PCR product length of 360bp to 520bp) and 10-repeats allele (480bp) detected was the dominant allele of DAT1 gene polymorphisms (90.6％) with the allele frequency 0.907. 6 genotypes were detected in this study and the genotype 480bp/480bp was the most common genotype (82.1％ ) with genotype frequency 0.821; ②No difference in distributions of frequencies of the genotypes and alleles were observed among ADHD group,control group and nuclear families ( all P ＞ 0.05). The scores of children in conduct, hyperactivity, attention deficit, hyperactivity index and total behavior scores in Conners-T in “non480bp/480bp” genotype in ADHD group were higher than those in“480bp/480bp” genotype in ADHD group, but there were no significant differences (all P ＞ 0.05 ). HRR and TDT analyses results for 54 ADHD nuclear families showed that no significant association was found between ADHD and DAT1 gene. Conclusion There isn' t significant association between DAT1 gene polymorphism and ADHD in Xi'an Han population. The 10-repeats allele(480bp) of DAT1 gene polymorphism may not be a risk factor of ADHD.