安替比林代谢产物形成速率的基因变异：一项针对未诱导双胞胎的研究。
Genetic variation in rates of antipyrine metabolite formation: a study in uninduced twins.
作者信息
Penno M B, Dvorchik B H, Vesell E S
出版信息
Proc Natl Acad Sci U S A. 1981 Aug;78(8):5193-6. doi: 10.1073/pnas.78.8.5193.
Abstract
Adult, male, unmedicated twins received antipyrine orally under carefully controlled environmental conditions. Relative contributions of genetic and environmental factors to 2-fold interindividual variations in rate constants for formation of the three main antipyrine metabolites were compared. Heritabilities for rate constants for formation of 4-hydroxyantipyrine, N-demethylantipyrine, and 3-hydroxymethylantipyrine were 0.88, 0.85, and 0.70, respectively. These results suggest that each molecular form of cytochrome P-450 that converts antipyrine to a different metabolite exhibits genetically controlled interindividual variations in activity. Unrelated adult male subjects whose environments were also carefully controlled exhibited highly reproducible rate constants for formation of antipyrine metabolites. Because the rate constant for metabolite formation sensitively detects certain variations in the gene product, it should be used in future pharmacogenetic studies on rates of production of multiple metabolites from a single parent drug.
摘要
成年男性同卵双胞胎在精心控制的环境条件下口服安替比林。比较了遗传因素和环境因素对三种主要安替比林代谢产物形成速率常数个体间2倍差异的相对贡献。4-羟基安替比林、N-去甲基安替比林和3-羟甲基安替比林形成速率常数的遗传率分别为0.88、0.85和0.70。这些结果表明，将安替比林转化为不同代谢产物的每种细胞色素P-450分子形式在活性上表现出遗传控制的个体间差异。环境也得到精心控制的无关成年男性受试者，其安替比林代谢产物形成的速率常数具有高度可重复性。由于代谢产物形成的速率常数能灵敏地检测基因产物中的某些变异，因此它应用于未来关于单一母体药物多种代谢产物生成速率的药物遗传学研究。
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