ADH single nucleotide polymorphism associations with alcohol metabolism in vivo
ADH single nucleotide polymorphism associations with alcohol metabolism in vivo
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DOI：
10.1093/hmg/ddp060
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发表时间：
2009-04-15
影响因子：
3.5
通讯作者：
Whitfield, John B.
中科院分区：
文献类型：
--
作者：
Birley, Andrew J.;James, Michael R.;Whitfield, John B.
我们以前发现，欧洲人酒精代谢的变化与含有ADH基因家族的染色体4q区域有关。我们现在已经在该地区分型了103个单核苷酸多态性（SNP），以测试酒精挑战后血液和呼吸酒精浓度变化的等位基因关联。体内酒精代谢建模与三个参数，确定吸收和酒精浓度的上升后摄入，和消除率。ADH 7 SNP的等位基因与酒精代谢的早期阶段相关，在ADH 1A，ADH 1B和ADH 4区域具有额外的影响。消除率与ADH 7和ADH 1C之间以及ADH 1C和ADH 1B之间基因内区域的SNP相关。影响酒精代谢的SNPs与报道的影响酒精依赖或酒精相关疾病的SNPs不一致。与早期和晚期代谢相结合的SNP关联仅占与ADH区域相关的总遗传方差的约20%，并且与该区域相关的体内酒精代谢的大部分方差尚未得到解释。
We have previously found that variation in alcohol metabolism in Europeans is linked to the chromosome 4q region containing the ADH gene family. We have now typed 103 single nucleotide polymorphisms (SNPs) across this region to test for allelic associations with variation in blood and breath alcohol concentrations after an alcohol challenge. In vivo alcohol metabolism was modelled with three parameters that identified the absorption and rise of alcohol concentration following ingestion, and the rate of elimination. Alleles of ADH7 SNPs were associated with the early stages of alcohol metabolism, with additional effects in the ADH1A, ADH1B and ADH4 regions. Rate of elimination was associated with SNPs in the intragenic region between ADH7 and ADH1C, and across ADH1C and ADH1B. SNPs affecting alcohol metabolism did not correspond to those reported to affect alcohol dependence or alcohol-related disease. The combined SNP associations with early- and late-stage metabolism only account for approximately 20% of the total genetic variance linked to the ADH region, and most of the variance for in vivo alcohol metabolism linked to this region is yet to be explained.