Known and novel sources of variability in the nicotine metabolite ratio in a large sample of treatment-seeking smokers.
Known and novel sources of variability in the nicotine metabolite ratio in a large sample of treatment-seeking smokers.
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DOI：
10.1158/1055-9965.epi-14-0427
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发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Tyndale RF
中科院分区：
文献类型：
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作者：
Chenoweth MJ;Novalen M;Hawk LW Jr;Schnoll RA;George TP;Cinciripini PM;Lerman C;Tyndale RF
3′羟基可替宁与可替宁的比值或尼古丁代谢物比值（NMR）与CYP2A6基因型、CYP2A6介导的尼古丁和可替宁代谢以及尼古丁清除率密切相关。更高的核磁共振（更快的尼古丁清除）与更重的吸烟和更低的戒烟率相关。目前正在研究核磁共振作为戒烟结果的预测性生物标志物（NCT01314001）。除了cyp2a6基因对核磁共振的强烈影响外，人口统计学和激素因素也会改变核磁共振。在这里，我们首次一起分析了在临床试验中筛选的吸烟者（N=1672）核磁共振变化的这些来源。参与者（平均年龄45.9岁）中，白人占65.1%，非裔美国人占34.9%，男性占54.8%。白种人的平均核磁共振（SD）高于非裔美国人(0.41（0.20）比0.33(0.21)；P<0.001)，女性vs男性(0.41(0.22)vs 0.37(0.20)；P < 0.001)。在女性中，使用避孕药（N=17）和激素替代疗法（N=14）分别与19.5% （P=0.09）和29.3% （P=0.06）的平均NMR升高相关，尽管没有显著性。BMI与NMR呈负相关（Rho= - 0.14， P<0.001），而饮酒（Rho=0.11， P<0.001）和吸烟（Rho=0.12， P<0.001）与NMR呈正相关。薄荷香烟使用者的核磁共振降低了16% （P<0.001）。当在线性回归模型中一起分析时，这些预测因子（每个≤2%）占总NMR变化的<8%。虽然这些因素显著影响NMR，但它们对总NMR变化的贡献很小（合计<8%，各≤2%）。因此，当使用核磁共振，例如前瞻性地指导戒烟治疗时，这些变异来源不太可能导致核磁共振错误分类。
The ratio of 3′hydroxycotinine to cotinine, or nicotine metabolite ratio (NMR), is strongly associated with CYP2A6 genotype, CYP2A6-mediated nicotine and cotinine metabolism, and nicotine clearance. Higher NMR (faster nicotine clearance) is associated retrospectively with heavier smoking and lower cessation rates. NMR as a predictive biomarker of cessation outcomes is being investigated (NCT01314001). In addition to strong CYP2A6-genetic influences on NMR, demographic and hormonal factors alter NMR. Here we analyzed, for the first time together, these sources of variation on NMR in smokers screened for this clinical trial (N=1672). Participants (mean age=45.9) were 65.1% Caucasian, 34.9% African American, and 54.8% male. Mean NMR (SD) was higher in Caucasians vs. African Americans (0.41(0.20) vs. 0.33(0.21); P<0.001), and in females vs. males (0.41(0.22) vs. 0.37(0.20); P<0.001). Among females, birth control pill use (N=17) and hormone replacement therapy (N=14) were associated with 19.5% (P=0.09) and 29.3% (P=0.06) higher mean NMR, respectively, albeit non-significantly. BMI was negatively associated with NMR (Rho=−0.14; P<0.001), while alcohol use (Rho=0.11; P<0.001) and cigarette consumption (Rho=0.12; P<0.001) were positively associated with NMR. NMR was 16% percent lower in mentholated cigarette users (P<0.001). When analyzed together in a linear regression model, these predictors (each ≤2%) accounted for <8% of total NMR variation. While these factors significantly affected NMR, they contributed little (together <8%; each ≤2%) to total NMR variation. Thus when using NMR, for example to prospectively guide smoking cessation therapy, these sources of variation are unlikely to cause NMR misclassification.