情感性精神障碍与5-羟色胺转运体基因的连锁不平衡研究

目的探讨情感性精神障碍与5-羟色胺转运体(5-HTT)基因之间的分子遗传学联系：方法以中国汉族人群中的72个情感性精神障碍核心家系(双相情感性精神障碍56例，重性抑郁症34例)作为研究对象，采用自编家系调查表、美国精神障碍诊断与统计手册第4版诊断标准并结合心理测评工具，应用聚合酶链反应(PCR)和限制性片段长度多态性分析方法，检测其5-HTT基因启动子区(5-HTTLPR)、第2内含子[数目可变的顺向重复(VNTR)]和3’端非编码区(3’UTRG／T)基因多态性，并进行连锁不平衡(TDT)分析。结果5-HTT基因中的VNTR与3’UTRG／T2个位点组合单体型与情感性精神障碍存在关联(TDT-x^2=4．08，经Monte Carlo逼真法1000次重复校正后的经验P值=0．04)，其他各位点5-HTTLPR、VNTR、3’UTRG／T等位基因与情感障碍未发现存在连锁不平衡，其他位点组合的单体型分析也未发现存在连锁不平衡。结论5-HTT基因在情感性精神障碍的遗传病因中可能起着一定作用。

The linkage disequilibrium study of the serotonin transporter gene and affective disorder

Objective To explore the association between affective disorder and serotonin transporter (5-HTT) gene. Methods Seventy-two parent-offspring trios with affective disorders (56 with bipolar disorders and 34 with major depression) were involved in the study. A self-compiled family questionnaire referred to the Family Interview for Genetic Studies and some psychological rating tools were used to assess the participants, and the diagnosis was made according to the 4th edition of Diagnostic and Statistical Manual of Mental Disorders Criteria. The genotypes of three polymorphisms (5-HTTLPR, 5-HTTVNTR and 5-HTT3'UTRG/T) in 5-HTT gene were determined by using polymerase chain reaction and restriction enzyme digestion techniques. The data were analyzed with family-based systemic linkage disequilibrium analysis. Results The VNTR-3' UTRG/T locus was associated with affective disorder (transmission/disequilibrium test-X2 = 4.08, P = 0. 04, P value was the empirical result corrected by Monte Carlo simulation after 1 000 replications). There were no linkage disequilibrium between other multi-marker loci (5-HTTLPR-VNTR, 5-HTTLPR-5-HTT3'UTRG/T and 5-HTTLPR-5-HTTVNTR-5-HTT3'UTRG/T) and affective disorder using the extended transmission disequilibrium test. Conclusion The 5-HTT gene may play a role in the onset of affective disorder.