Culverhouse Robert C, Johnson Eric O, Breslau Naomi, Hatsukami Dorothy K, Sadler Brooke, Brooks Andrew I, Hesselbrock Victor M, Schuckit Marc A, Tischfield Jay A, Goate Alison M, Saccone Nancy L, Bierut Laura J
Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA; Division of Biostatistics, Washington University School of Medicine, Saint Louis, MO, USA.
Addiction. 2014 May;109(5):814-22. doi: 10.1111/add.12478. Epub 2014 Feb 18.
Studies have shown association between common variants in the α6-β3 nicotinic receptor subunit gene cluster and nicotine dependence in European ancestry populations. We investigate whether this generalizes to African Americans, whether the association is specific to nicotine dependence and whether this region contains additional genetic contributors to nicotine dependence.
We examined consistency of association across studies and race between the α6β3 nicotinic receptor subunit locus and nicotine, alcohol, marijuana and cocaine dependence in three independent studies.
United States of America.
European Americans and African Americans from three case-control studies of substance dependence.
Subjects were evaluated using the Semi-Structured Assessment for the Genetics of Alcoholism. Nicotine dependence was determined using the Fagerström Test for Nicotine Dependence.
The single nucleotide polymorphism rs13273442 was associated significantly with nicotine dependence across all three studies in both ancestry groups [odds ratio (OR) = 0.75, P = 5.8 × 10(-4) European Americans; OR = 0.80, P = 0.05 African Americans]. No other substance dependence was associated consistently with this variant in either group. Another SNP in the region, rs4952, remains modestly associated with nicotine dependence in the combined data after conditioning on rs13273442.
The common variant rs13273442 in the CHRNB3-CHNRA6 region is associated significantly with nicotine dependence in European Americans and African Americans across studies recruited for nicotine, alcohol and cocaine dependence. Although these data are modestly powered for other substances, our results provide no evidence that correlates of rs13273442 represent a general substance dependence liability. Additional variants probably account for some of the association of this region to nicotine dependence.
研究表明，α6-β3烟碱受体亚基基因簇中的常见变异与欧洲血统人群的尼古丁依赖之间存在关联。我们调查这种关联是否适用于非裔美国人，该关联是否特定于尼古丁依赖，以及该区域是否包含导致尼古丁依赖的其他遗传因素。
我们在三项独立研究中，检验了α6β3烟碱受体亚基基因座与尼古丁、酒精、大麻和可卡因依赖之间在不同研究及种族中的关联一致性。
美国。
来自三项物质依赖病例对照研究的欧裔美国人和非裔美国人。
使用酒精中毒遗传学半结构化评估对受试者进行评估。使用尼古丁依赖Fagerström测试确定尼古丁依赖。
在两项血统组的所有三项研究中，单核苷酸多态性rs13273442均与尼古丁依赖显著相关[比值比（OR）=0.75，P=5.8×10⁻⁴，欧裔美国人；OR=0.80，P=0.05，非裔美国人]。两组中没有其他物质依赖与该变异始终相关。在以rs13273442为条件的合并数据中，该区域的另一个单核苷酸多态性rs4952仍与尼古丁依赖存在适度关联。
在针对尼古丁、酒精和可卡因依赖开展的多项研究中，CHRNB3-CHNRA6区域的常见变异rs13273442与欧裔美国人和非裔美国人的尼古丁依赖显著相关。尽管这些数据对其他物质的检验效力较低，但我们的结果没有提供证据表明rs13273442的相关性代表一般的物质依赖易感性。其他变异可能是该区域与尼古丁依赖之间部分关联的原因。
