5-羟色胺转运体基因第2内含子VNTR与情感性精神障碍的连锁不平衡分析

Association analysis between affective disorder and polymorphism within intron 2 of the human serotonin transporter gene

目的探讨5-羟色胺转运体基因第2内含子VNTR(5-HTTVNTR)位点多态性与情感性精神障碍之间的分子遗传学联系。方法在中国汉族人群中,以情感性精神障碍核心家系作为研究对象,根据美国哈佛大学提供的遗传学研究用诊断性检查表(DIGS)自编家系调查表,采用中国精神疾病分类与诊断标准(CCMD-3)并结合一些心理测评工具,以达到表型一致。在72个情感性精神障碍核心家系的222个家系成员(其中双相情感性精神障碍56例,重性抑郁症34例)中,应用聚合酶链反应(PCR)和限制性片段长度多态性方法,对5-HTTVNTR位点多态性与情感性精神障碍之间的分子遗传学联系进行了以家系为基础的连锁不平衡分析。结果基因型和等位基因频率在情感性精神障碍患者组和父母组之间无显著差异。GHRR和HHRR分析以及多等位基因ETDT统计分析也未发现存在连锁不平衡。5-HTTVNTR位点仅扩增出12和10拷贝两种形式的等位基因片段,其中等位片段12的频率为88%。结论5-HTTVNTR位点多态性在情感性精神障碍疾病的发病中可能不起重要作用。

Objective To explore the association between affective disorder and polymorphism within intron 2 of the human 5-HTT gene. Methods The study selected affective disorder parent-offspring trios as research subjects and investigated with self-editing family question naire according to Diagnostic Investigation Genet Scale (DIGS) provided by Harvard University and adopting Chinese Diagnostic Criterion CCMD-3 (Chinese Classification and Diagnostic Criteria of Disorder 3rd version), and combining with some psychological rating tools to reach phenotypes consistency. Genomic DNA was isolated from 72 core pedigrees, sum to 222 family members (including 56 bipolar disorders and 34 major depressions). The genotype was carried out using polymerase chain reaction (PCR) and restriction fragment length polymorphism techniques. A family-based linkage disequilibrium analysis was conducted. Results There are no significant differences between parent group and patient group from 70 integrity core pedigree members of Chinese Han nationality (including 70 affective disorder probands, 222 parents) in genotype and allele gene frequency of 5-HTT VNTR by case-parent control study .The GHRR, HHRR and the TDT of multiple allele all did not show association between affective disorder and this polymorphism locus in the 5-HTT gene. However, the polymorphism locus of the intron 2 in 5-HTT gene was only amplified two forms of allele fragment 12 and 10. Among this allele fragments, the allele frequency is up to 88%. Conclusion Our preliminary results suggest that The VNTR polymorphism does not play a major role in the onset of affective disorder.