Department of Neurology, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA.
Addict Biol. 2012 Jan;17(1):181-91. doi: 10.1111/j.1369-1600.2010.00265.x. Epub 2010 Nov 11.
Previous studies of the association of the C17T polymorphism of the mu opiate receptor gene with substance dependence compared cases with substance dependence to controls and usually found no significant association. However, the studies were limited by small sample size-no study had more than 12 subjects with the TT genotype, a genotype that is rare in white and Asian subjects. Moreover, drug use is not dichotomous but follows a spectrum from non-use to modest, intermittent use, to use several times daily. We asked whether the Kreek-McHugh-Schluger-Kellogg (KMSK) scales for alcohol, cocaine, opiates and tobacco that quantify substance use during the time of a subject's maximal use might be more sensitive measures than dichotomous outcomes. We administered the KMSK scales and completed C17T genotyping on 1009 human immunodeficiency virus (HIV)-infected and 469 HIV-uninfected women in The Women's Interagency HIV Study, an ongoing study of HIV in women. Forty-two of the 697 African American, 1 of the 182 Hispanic and none of the 161 white women had the TT genotype. KMSK cocaine, alcohol and tobacco scores were significantly higher in the African American women with the TT genotype (P = 0.008, 0.0001, and 0.006, respectively), but opiate scores were not. Ordinal regression models controlling for HIV serostatus, age, education, and income had odds ratios for the TT genotype for predicting alcohol, tobacco, cocaine and opiates scores of 2.1 (P = 0.02), 2.4 (P = 0.0004), 2.0 (P = 0.03) and 1.9 (P = 0.07). We conclude that the TT genotype of OPRM1 may increase the risk of substance use and abuse.
先前有关μ阿片受体基因 C17T 多态性与物质依赖相关性的研究,将物质依赖患者与对照者进行了比较,通常未发现显著相关性。然而,这些研究受到样本量小的限制——没有研究纳入超过 12 名 TT 基因型的受试者,而 TT 基因型在白人和亚洲人群中较为罕见。此外,药物使用并非二分法,而是呈现出从非使用到适度、间歇性使用,再到每日多次使用的连续谱。我们想知道,Kreek-McHugh-Schluger-Kellogg(KMSK)量表是否比二分法结果更敏感,该量表可定量评估受试者使用物质的高峰期的物质使用情况,用于评估酒精、可卡因、阿片类药物和烟草。我们对 1009 名感染人类免疫缺陷病毒(HIV)的妇女和 469 名未感染 HIV 的妇女进行了 KMSK 量表评估和 C17T 基因分型,这些妇女均为 Women's Interagency HIV Study 的参与者,该研究正在进行中。在非洲裔美国妇女中,42 名(占 697 名)、1 名(占 182 名)和无 1 名(占 161 名)白人妇女具有 TT 基因型。携带 TT 基因型的非洲裔美国妇女的 KMSK 可卡因、酒精和烟草评分显著较高(P=0.008、0.0001 和 0.006),但阿片类药物评分无差异。控制 HIV 血清状态、年龄、教育和收入的有序回归模型显示,TT 基因型预测酒精、烟草、可卡因和阿片类药物评分的比值比分别为 2.1(P=0.02)、2.4(P=0.0004)、2.0(P=0.03)和 1.9(P=0.07)。综上,OPRM1 的 TT 基因型可能增加物质使用和滥用的风险。