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首页> 外文期刊>Addiction biology >Association of ADH4 genetic variants with alcohol dependence risk and related phenotypes: results from a larger multicenter association study.
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Association of ADH4 genetic variants with alcohol dependence risk and related phenotypes: results from a larger multicenter association study.

机译：ADH4遗传变异与酒精依赖风险和相关表型的关联：一项更大的多中心关联研究的结果。

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摘要

Genetic variants of the alcohol-metabolizing enzyme ADH4, located on chromosome 4q22-4q23, have been related to alcohol dependence (AD) risk in previous research. The aim of this association study in a large multicenter sample of alcohol-dependent individuals and controls is to confirm ADH4 single nucleotide polymorphism (SNP) and haplotype association with AD and relevant related phenotypes. One thousand, six hundred and twenty-two (1622) inpatient subjects and 1469 control subjects with DSM-IV. AD from four addiction treatment centres were included. Characteristics of AD and related phenotypes including alcohol withdrawal, Cloninger's type I and II and first ages of drinking, regular drinking and AD onset were obtained using standardized structured interviews. After subjects were genotyped for 2 ADH4 polymorphisms, single SNP case-control and haplotype analyses were conducted. Both variants--rs1800759 and rs1042364--and the A-A and C-G haplotypes were significantly related to AD across samples. Furthermore, associations with AD-related phenotypes and subtypes revealed a potential protective influence of this haplotype. This study confirms the significant relationship of ADH4 variants with AD and related phenotypes. While the rs1800759 and rs1042364 A-A haplotype had a potential protective influence on the risk for several AD-related phenotypes, this effect is rather small compared to functional variants of other alcohol or acetaldehyde-metabolizing enzymes like ALDH2*2 or ADH1B*2.
机译：在先前的研究中，位于4q22-4q23染色体上的酒精代谢酶A​​DH4的遗传变异与酒精依赖（AD）风险有关。在酒精依赖型个体和对照的大型多中心样本中进行这项关联研究的目的是确认ADH4单核苷酸多态性（SNP）和单倍型与AD及相关相关表型的关联。 DSM-IV的住院患者为1,262名（1622）和1469名对照受试者。包括来自四个成瘾治疗中心的AD。使用标准的结构化访谈获得AD和相关表型的特征，包括戒酒，克隆宁I型和II型以及首次饮酒年龄，经常饮酒和AD发作。对受试者进行2种ADH4多态性的基因分型后，进行单SNP病例对照和单倍型分析。 rs1800759和rs1042364-这两个变体以及A-A和C-G单倍型均与样品中的AD显着相关。此外，与AD相关的表型和亚型的关联揭示了该单倍型的潜在保护作用。这项研究证实了ADH4变体与AD和相关表型的显着关系。尽管rs1800759和rs1042364 A-A单倍型对几种AD相关表型的风险具有潜在的保护作用，但与其他酒精或乙醛代谢酶（如ALDH2 * 2或ADH1B * 2）的功能性变体相比，这种影响很小。

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