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首页> 外文期刊>Pharmacogenetics and genomics >Genetic and environmental influences on the ratio of 3'hydroxycotinine to cotinine in plasma and urine.
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Genetic and environmental influences on the ratio of 3'hydroxycotinine to cotinine in plasma and urine.

机译：遗传和环境对血浆和尿液中3'羟基烟碱与可替宁比率的影响。

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OBJECTIVES: The ratio of trans-3'hydroxycotinine/cotinine (3HC/COT) is a marker of CYP2A6 activity, an important determinant of nicotine metabolism. This analysis sought to conduct a combined genetic epidemiologic and pharmacogenetic investigation of the 3HC/COT ratio in plasma and urine. METHODS: One hundred and thirty-nine twin pairs [110 monozygotic and 29 dizygotic] underwent a 30-min infusion of stable isotope-labelled nicotine and its major metabolite, cotinine, followed by an 8-h in-hospital stay. Blood and urine samples were taken at regular intervals for analysis of nicotine, cotinine, and metabolites. DNA was genotyped to confirm zygosity and for variation in the gene for the primary nicotine metabolic enzyme, CYP2A6 (variants genotyped: *1B, *1 x 2, *2, *4, *9, *12). Univariate biometric analyses quantified genetic and environmental influences on each measure in the presence and absence of covariates, including measured CYP2A6 genotype. RESULTS: There was a substantial amount of variation inthe free 3HC/COT ratio in plasma (6 h postinfusion) attributable to additive genetic influences (67.4%, 95% confidence interval=55.9-76.2%). The heritability estimate was reduced to 61.0 and 49.4%, respectively, after taking into account the effect of covariates and CYP2A6 genotype. In urine (collected over 8 h), the estimated amount of variation in the 3HC/COT ratio attributable to additive genetic influences was smaller (47.2%, 95% confidence interval=0-67.2%) and decreased to 44.6 and 42.0% after accounting for covariates and genotype. CONCLUSION: Additive genetic factors are prominent in determining variation in plasma 3HC/COT but less so in determining variation in urine 3HC/COT.
机译：目的：反式3'羟基烟碱/烟碱的比率（3HC / COT）是CYP2A6活性的标志，CYP2A6活性是烟碱代谢的重要决定因素。该分析试图对血浆和尿液中的3HC / COT比率进行遗传流行病学和药物遗传学研究。方法：对139对双胞胎[110个单卵双生和29个双卵双生]进行了30分钟的稳定同位素标记烟碱及其主要代谢产物可替宁的输注，然后在医院住院了8小时。定期抽取血液和尿液样本，以分析尼古丁，可替宁和代谢产物。对DNA进行基因分型以确认接合性，并确定主要尼古丁代谢酶CYP2A6的基因变异（基因型变异：* 1B，* 1 x 2，* 2，* 4，* 9，* 12）。在存在和不存在协变量（包括测得的CYP2A6基因型）的情况下，单变量生物特征分析可量化对每种测量的遗传和环境影响。结果：血浆中游离3HC / COT比例（输注后6小时）有很大的变化，这归因于加性遗传影响（67.4％，95％置信区间= 55.9-76.2％）。考虑到协变量和CYP2A6基因型的影响，遗传力估计值分别降至61.0％和49.4％。在尿液（收集超过8小时）中，归因于累加遗传影响的3HC / COT比值的估计变化量较小（47.2％，95％置信区间= 0-67.2％），经核算后降至44.6和42.0％用于协变量和基因型。结论：加性遗传因素在确定血浆3HC / COT变异中很突出，但在确定尿液3HC / COT变异中不那么重要。

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