自杀未遂与5-羟色胺转运体基因的连锁不平衡研究

摘要

目的 探讨自杀未遂与5-羟色胺转运体(5-HTT)基因之间的分子遗传学关系.方法 以重庆地区汉族人群中自杀未遂核心家系作为研究对象,采集86个核心家系的258个家系成员的肘静脉血,将其分为患者组与父母组.应用聚合酶链反应(PCR)和限制性片段长度多态性方法,研究5-HTT基因启动子区多态性(5-HTTLPR)、5-HTT基因第二内含子多态性(5-HTTVNTR)与自杀未遂之间的分子遗传学关系,并进行基于单体型的单体型相对风险(HHRR)分析及连锁不平衡(TDT)分析.结果 父母组和患者组的5-HTTLPR、5-HTTVNTR基因型及等位基因频率的总体分布比较差异均无统计学意义(P＞0.05).HHRR分析结果显示患者组与虚拟对照组的5-HTTLPR、5-HTTVNTR基因频率差异均无统计学意义(P＞0.05).多等位基因TDT统计分析显示86个核心家系分别有54及89个杂合子父母纳入5-HTTLPR、5-HTTVNTR的统计,5-HTTLPR、5-HTTVNTR与自杀未遂间不存在连锁不平衡(P＞0.05).在5-HTT基因的2个多态性位点组合成的4种单体型中进行单体型分析,组间差异均无统计学意义(P＞0.05),提示自杀未遂患者与这2个位点形成的单体型不存在传递上的偏倚.结论 5-HTT基因不是自杀未遂的主要遗传基因.%Objective To discuss the molecular genetics correlation between suicide attempts and 5 hydroxytryptamine trans porter(5-HTT) gene. Methods Nuclear family with suicide attempts of Han nationality in Chongqing area was served as research object. Cubital venous blood were collected from 258 members in 86 nuclear families,and they were divided into patient group and parents goup. Polymerase chain reaction(PCR) and restriction fragment length polymorphism method were employed to study the molecular genetics correlation between serotonin-transporter linked polymorphic region(5 HTTLPR) or serotonin transporter gene2 VNTR polymorphism(5-HTTVNTR) and suicide attempts,and haplotype-based haplotype relative risk(HHRR) and transmission disequilibrium test(TDT) analysis were conducted. Results Differences of overall distribution of 5-HTTLPR, 5-HTTVNTR polymorphism genotype and allele frequencies between parents goup and patient group showed no statistically significant (P＞ 0.05). HHRR analysis demonstrated that there was no statistically significant difference in allele frequencies of 5 HTTLPR and 5 HTTVNTR between patient group and the virtual control group(P＞0.05). Multi-allele TDT statistical analysis showed that there were 54 and 89 heterozygous parents from 86 nuclear families were recruited to conduct 5 HTTLPR and 5-HTTVNTR analysis,respectively. Both 5-HTTLPR and 5-HTTVNTR showed no linkage disequilibrium with suicide attempts(P＞0.05). Analyzing 4 haplotypes composed of 2 polymorphic sites of 5-HTT gene showed no statistically significant difference among them(P＞0.05),suggesting that biased transmission did not exist in patients with suicide attempts and haplotypes composed of these 2 polymorphicsites. Conclusion 5-HTT gene is not a major gene involving suicide attempts.