Interaction between the functional polymorphisms of the alcohol-metabolism genes in protection against alcoholism
Interaction between the functional polymorphisms of the alcohol-metabolism genes in protection against alcoholism
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DOI：
10.1086/302540
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发表时间：
1999-09-01
影响因子：
9.8
通讯作者：
Yin, SJ
中科院分区：
文献类型：
--
作者：
Chen, CC;Lu, RB;Yin, SJ
编码酒精代谢主要酶醇脱氢酶（ADH）和醛脱氢酶（ALDH）的基因表现出功能多态性。编码高活性ADH亚型的变异等位基因ADH2*2和ADH3*1，以及编码低活性ALDH2亚型的ALDH2*2等位基因，可以防止东亚人酗酒。为了研究这些保护基因之间可能的相互作用，我们对生活在台湾的340名酗酒者和545名对照汉人的ADH2、ADH3和ALDH2位点进行了基因分型。控制ALDH2*2的影响后，多元logistic回归分析显示，ADH3等位基因变异对酒精中毒风险无显著影响。这可以通过ADH3*1和ADH2*2之间的连锁不平衡来解释，无论ADH2基因型如何，ALDH2*2的纯合性都能完全防止酒精中毒；在嗜酒者中没有发现这种纯合性。对ADH2和ALDH2基因座剩余6个组合基因型的Logistic回归分析表明，与ADH2*1/*1和ALDH2*1/*1基因型相比，携带1个或2个ADH2*2基因型和携带1个ALDH2*2基因型的个体酒精中毒风险最低（or 0.04-0.05）。与ADH2*2/*2- aldh2 *1/*1基因型相关的疾病风险约为与ADH2*2/*2- aldh2 *1/*1基因型相关的疾病风险的一半。结果表明，ADH2*2等位基因提供的保护可能独立于ALDH2*2提供的保护。
The genes that encode the major enzymes of alcohol metabolism, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), exhibit functional polymorphism. The variant alleles ADH2*2 and ADH3*1, which encode high-activity ADH isoforms, and the ALDH2*2 allele, which encodes the low-activity form of ALDH2, protect against alcoholism in East Asians. To investigate possible interactions among these protective genes, we genotyped 340 alcoholic and 545 control Han Chinese living in Taiwan at the ADH2, ADH3, and ALDH2 loci. After the influence of ALDH2*2 was controlled for, multiple logistic regression analysis indicated that allelic variation at ADH3 exerts no significant effect on the risk of alcoholism. This can be accounted for by linkage disequlibrium between ADH3*1 and ADH2*2 ALDH2*2 homozygosity, regardless of the ADH2 genotypes, was fully protective against alcoholism; no individual showing such homozygosity was found among the alcoholics. Logistic regression analyses of the remaining six combinatorial genotypes of the polymorphic ADH2 and ALDH2 loci indicated that individuals carrying one or two copies of ADH2*2 and a single copy of ALDH2*2 had the lowest risk (ORs 0.04-0.05) for alcoholism, as compared with the ADH2*1/*1 and ALDH2*1/*1 genotype. The disease risk associated with the ADH2*2/*2-ALDH2*1/*1 genotype appeared to be about half of that associated with the ADH2*2/*2-ALDH2*1/*1 genotype. The results suggest that protection afforded by the ADH2*2 allele may be independent of that afforded by ALDH2*2.