Effects of aldehyde dehydrogenase-2 genetic polymorphisms on metabolism of structurally different aldehydes in human liver
Effects of aldehyde dehydrogenase-2 genetic polymorphisms on metabolism of structurally different aldehydes in human liver
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DOI：
10.1124/dmd.30.1.69
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发表时间：
2002-01-01
影响因子：
3.9
通讯作者：
Honma, T
中科院分区：
文献类型：
--
作者：
Wang, RS;Nakajima, T;Honma, T
采用改进的简化方法对醛脱氢酶(ALDH)-2基因进行基因型分析，并研究了该基因型对人肝细胞不同部位多种醛代谢的影响。还分析了性别、年龄、吸烟、饮酒、肝功能和各种药物对ALDH活性的影响。39例受试者中，8例为野生等位基因（ALDH2*1）与突变等位基因（ALDH2*2）杂合子，其余为野生等位基因（ALDH2*2）纯合子。携带突变等位基因的受试者肝脏线粒体中ALDH对乙醛的活性低于携带两个野生型等位基因的10%，并且ALDH2*1/*2组对甲醛、丙醛、正丁醛、己二醛和七醛的活性也显著低于ALDH2*1/*1组。然而，辛醛、癸醛、视黄醛、苯甲醛、3-羟基苯甲醛和2,5-二羟基苯甲醛在两个基因型中的代谢相似。细胞质部分的活性变化与线粒体相似。两组小鼠微粒体ALDH活性差异无统计学意义。肝脏匀浆上清中ALDH对乙醛和其他短链脂肪醛的总活性受到类似于线粒体的影响。我们的研究结果表明，ALDH2基因的单核苷酸多态性仅改变短脂肪链醛的代谢。此外，性、饮酒和吸烟对ALDH活性几乎没有影响，尽管老年人的活性往往较低，但统计上不显著。
Genotype analysis of the aldehyde dehydrogenase (ALDH)-2 gene was performed using an improved simplified method, and effects of the genotype on the metabolism of a variety of aldehydes in different fractions of human liver cells were investigated. The effects of sex, aging, smoking, drinking alcohol, liver function, and various drugs on ALDH activity were also analyzed. Of the 39 subjects, eight were heterozygotes of the wild (ALDH2*1) and mutant (ALDH2*2) alleles, and the others were homozygotes of the wild allele. ALDH activity toward acetaldehyde in liver mitochondria from subjects with a mutant allele was less than 10% of that with two alleles of wild-type, and the activities toward formaldehyde, propionaldehyde, n-butyraldehyde, capronaldehyde, and heptaldehyde were also significantly lower in the ALDH2*1/*2 rather than ALDH2*1/*1 group. However, the metabolism of octylaldehyde, decylaldehyde, retinaldehyde, benzaldehyde, 3-hydroxybenzaldehyde, and 2,5-dihydroxybenzaldehyde was similar in the two genotypes. Changes in activity in the cytosolic fraction were similar to those in mitochondria. There was no significant difference in ALDH activity in microsomes between the two groups. Total activities of ALDH toward acetaldehyde and other short-chain aliphatic aldehydes in supernatant fractions of homogenized liver were affected in a manner similar to that in mitochondria. Our results suggest that the single nucleotide polymorphisms of the ALDH2 gene only alter the metabolism of aldehydes with a short aliphatic chain. Furthermore, sex, drinking alcohol, and smoking had little effect on ALDH activity, although the activity in elderly individuals tended to be lower albeit statistically insignificant.