酒精代谢相关基因位点多态性与酒依赖风险及酒精主观反应的关系

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目的:探讨酒精代谢酶及药效酶基因ALDH2(rs671)、ADH1B(rs1229984)、ADH1C(rs141973904)、OPRM1(rs1799971)、PDYN(rs1997794)位点多态性与个体的酒精主观反应、饮酒行为之间的关系。方法:选取2018年1~12月在新疆医科大学第一附属医院及新疆精神卫生中心住院且符合DSM-Ⅳ诊断的酒依赖患者(酒依赖组,n n=100)。酒依赖组与正常健康被试(对照组,n n=100)完成一般情况调查表、签署知情同意书,抽取静脉血5 ml提取DNA,酒依赖组完成酒精挑战试验,于饮酒前、饮酒后30、60、120、180 min分别完成双相酒精反应问卷(biphasic alcohol effect scale,BAES)、药物效应问卷(drug effect questionaire,DEQ)。利用效用程序计算遗传连锁分析的Hardy-Weinberg平衡。采用Pearson卡方检验并计算优势比n OR值,使用重复测量卡方检验法分析个体酒精主观反应的变化趋势。n 结果:rs671等位基因位点A与酒依赖的风险相关(χn 2=23.97,n P<0.01,n OR=7.11,95%n CI=2.93~17.30),rs1229984位点单核苷酸多态生以显性遗传模型“T/T-C/T”为最佳拟合模型(n P<0.01,n OR=0.16,95%n CI=0.08~0.32),是酒依赖的保护性因素。酒依赖患者rs1229984位点基因型TT者较CC和CT者的个体最大饮酒量(n F=4.86,n P=0.01)、每周饮酒量(n F=4.51,n P=0.01)更低,rs1799971位点基因型GG与GA者的个体最大饮酒量(n F=20.28,n P<0.01)、周饮酒量(n F=12.46,n P<0.01)均大于AA型者。rs1799971位点基因型AA者较GG及GA者表现出更低的兴奋作用(n F=7.99,n P=0.01)、更高的镇静作用(n F=57.04,n P<0.01)及更低的“喜欢”(n F=13.38,n P<0.01)和“还想要一些”(n F=26.37,n P<0.01)效应。n 结论:酒精代谢酶rs671、rs1229984基因多态性与个体饮酒行为、饮酒量关系密切,rs1799971既与个体饮酒行为有关,又与饮酒后主观反应关系有关。“,”Objective:To explore the relationship between rs671 (ALDH2), rs1229984 (ADH1B), RS141973904 (ADH1C), RS1799971 (OPRM1), rs1997794 (PDYN) polymorphism and individual's alcohol subjective response and drinking behavior.Methods:From January to December 2018, patients with alcohol dependence who were hospitalized in the First Affiliated Hospital of Xinjiang Medical University and Xinjiang mental health center and met the DSM-IV were selected (alcohol dependence group, n n=100). Alcohol dependence patients and normal healthy subjects (control group, n n=100) completed general demographic questionnaire, including drinking behavior such as the frequency of drinking each week and the maximum alcohol consumption at one drink, and informed consent, then were extracted of venous blood for DNA test.After that, alcoholics completed the alcohol challenge test.Biphasic alcohol effect scale(BAES) and drug effect questionnaire (DEQ) were completed before drinking and after drinking 30, 60, 120, 180 minutes respectively.Hardy-Weinberg equilibrium for genetic linkage analysis was calculated by utility program.Pearson Chi-square test was used to analyze the odds ratio(OR) value, and the chi-square test of repeated measured variables were used to analyze the variation trend of individual subjective response to alcohol after drinking.n Results:rs671 allele A was associated with alcohol dependence risk (χn 2=23.97, n P<0.01,n OR=7.11, 95%n CI=2.93~17.30), and for rs1229984 polymorphism the dominant genetic model “ T/T-C/T” was taken as the best fitting model ( n P<0.01,n OR=0.16, 95%n CI=0.08-0.32), which was a protective factor for alcohol dependence.Alcoholics with TT genotype in rs1229984 had lower maximum alcohol consumption (n F=4.86, n P=0.01) and weekly alcohol consumption (n F=4.51, n P=0.01) than those with CC and CT genotype.The maximum alcohol consumption (n F=20.28, n P<0.01) and weekly alcohol consumption (n F=12.46, n P<0.01) of individuals with GG and GA genotype in rs1799971 were higher than those with AA genotype.The AA genotype of rs1799971 showed lower stimulative effect (n F=7.99, n P=0.01), higher sedative effect (n F=57.04, n P<0.01), and lower “ like” (n F=13.38, n P<0.01) and “ more” effect (n F=26.37, n P<0.01) than that with GG and GA genotype.n Conclusion:rs671 and rs1229984 are more closely related to individual drinking behavior and volume of alcohol consumption.rs1799971 is not only related to individual drinking behavior, but also has a more closed relationship with subjective response to alcohol.
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