Aldh2 Deficiency--population Genetics /Phenotype

在东方人中，由于常见的Glu487Lys多态性导致的ALDH2缺乏经常在饮酒后引起脸红反应，这种厌恶反应是具有不活跃的Lys487等位基因的个体酒精中毒率较低的原因。R. Peterson在ALDH2上发现了一系列额外的标记。通过限制性内切酶分析、SSCP和测序，鉴定了两个ALDH2等位基因的单倍型特征。该分析揭示了Lys487等位基因的起源和功能作用，该等位基因似乎起源于单一单倍型谱系，并在东亚人群中传播。此外，尽管它可能起源于单一遗传背景，但单倍型分析显示，该突变足够古老，因此随后发生了其他突变。ALDH2单倍型的结果与保持东方ALDH2变异Glu487Lys的选择效应最为一致。我们正在研究ADH和ALDH功能等位基因与酒精中毒和其他药物滥用表型的关系。这些基因型/表型关系正在与其他基因座结合研究，例如阿片类药物成瘾中的OPRM1受体位点。我们对ADH和ALDH基因的两个snp进行了基因分型，并分析了中国大量样本中ADH和ALDH基因与海洛因滥用的关系。结果显示ADH、ALDH与中国阿片类药物成瘾者之间没有关联。OPRM、118A到G、OPRD、307T到C snp与阿片类药物成瘾也没有关联。

In Orientals, ALDH2 deficiency due to the common polymorphism Glu487Lys frequently causes a flushing reaction after alcohol consumption and this aversive reaction is responsible for lower rates of alcoholism in individuals with the inactive Lys487 allele. R. Peterson identified a series of additional markers at ALDH2. By restriction enzyme analysis, SSCP, and sequencing, haplotypes characteristic for the two ALDH2 alleles were identified. This analysis has shed light on the origins and functional role of the Lys487 allele, which appears to have originated once, on a single haplotype lineage, and spread among East Asian populations. Furthermore, although it probably originated on a single genetic background, haplotype analysis reveals that the mutation was sufficiently ancient for additional mutations to have occurred subsequently. The results on ALDH2 haplotypes are most compatible with an effect of selection to maintain the Oriental ALDH2 variant, Glu487Lys. We are investigating the relationship of ADH and ALDH functional alleles to alcoholism and other substance abuse phenotypes. These genotype/phenotype relationships are being studied in combination with other loci, for example the OPRM1 receptor locus in opioid addiction. We genotyped two SNPs of ADH and ALDH gene and analyzed the association with heroin abuse in a large Chinese sample. The results have shown no association between ADH, ALDH, and Chinese opioid addicted subjects. There is also no association between OPRM, 118A to G, OPRD, 307T to C SNPs and opioid addicts.