云南汉族酒精依赖综合征与COMT遗传多态性的关联研究

目的：研究儿茶酚胺氧位甲基转移酶（COMT）的不同基因型及等位基因频率在云南汉族酒精依赖综合征患者组和健康对照组的分布差异。方法：应用聚合酶链式反应．限制性片段长度多态性分析法，对COMT基因的rs2075507、rs737865、rs4680、rsl65599四个基因位点进行特异性扩增，限制性内切酶酶切分型。结果：上述4个候选基因中，COMT基因rs737865位点C／C基因型频率在健康对照组较酒依赖组高，其基因型分布在两组中有差异，且具有统计学意义（P〈0．05）。其余3个位点统计学分析均无显著性差异（P〉0．05）。单倍型分析：上述四个候选基因构建出12种主要单倍型（每种单倍型在对照组和酒依赖组中的频率至少有一个大于1％），单倍型A—C—A—A有可能是云南汉族酒精依赖发生的一种危险因子（OR：2．865，P=0．003347）。连锁不平衡分析显示：云南汉族人群中，COMT基因的rs2075507和rs737865之间存在着强连锁（D〉0．8）。结论：在云南汉族人群中，COMT基因rs2075507、rs4680和rs165599位点与酒依赖无关联性，rs737865C／C基因型可能是酒精依赖的保护因子，可能降低嗜酒的发生率。单倍型A-C-A-A有可能是云南汉族酒精依赖发生的一种危险因子。云南汉族人群中，COMT基因的rs2075507和rs737865之间存在着强连锁。

Association Analysis of Alcohol Dependence Syndrome Among Han Population in Yunnan with Genetic Polymorphisms of COMT

Objective： To study the difference of genotype and allele frequencies of catechol-o-methyltransferase （COMT） gene between alcohol dependent group and control group among the Han population in Yunnan. Methods： The portions of rs2075507, rs737865, rs4680, rs165599 of COMT gene are amplified by using Polymerase chain reaction-restricted fragments length polymorphism technique （PCR-RFLP）. An aliquot of the amplified DNA fragments are treated with restriction end nucleases. Results： The genotype frequencies ofCOMT gene rs737865 polymorphism differ significantly between alcohol dependence group and control group （P〈0.05）. The frequency of C/C genotype in control group is higher than alcohol dependent group. The frenquencise of other genotype and allele between alcohol dependence group and control group have no statistic significance （P 〉0.05）. Logistic regression analysis shows C/C genotype is associated positively with alcohol dependence （OR：0.822 ,P 〉0.05） ,it has no statistic significance.The analysis results of haplotypes for rs2075507-rs737865-rs4680-rs165599 as follows：we find that there are 12 major haplotypes in Yunnan Han population （frequency of each haplotype is greater than 1% at least in one group）, A-C-A-A haplotype may be a dangerous factor leading to alcohol dependence syndrome （OR：2.865,P=0.003347）. Linkage disequilibrium analysis shows that there are strong linkage between rs2075507 and rs737865 in Yunna Han population （D 〉0.8）. Conclusions： There is no significant association in rs2075507,rs4680 and rs165599 between alcohol dependence patients and normal controls in Yunna Han population.rs737865 gene polymorphism has an association with alcohol dependence,C/C genotype is associated positively with alcohol dependence. A-C-A-A haplotype may be a dangerous factor leading to alcohol dependence syndrome. There is strong linkage between rs2075507 and rs737865 in Yunna Han population.