Division of Family & Community Medicine, Department of Medicine, Center for Education in Family & Community Medicine, Stanford University School of Medicine, 1215 Welch Road, Modular G, Stanford, CA 94305-5408, USA.
Nicotine Tob Res. 2010 Mar;12(3):251-62. doi: 10.1093/ntr/ntp201. Epub 2010 Feb 4.
The 11q23.1 genomic region has been associated with nicotine dependence in Black and White Americans.
By conducting linkage disequilibrium analyses of 7 informative single nucleotide polymorphisms (SNPs) within the tetratricopeptide repeat domain 12 (TTC12)/ankyrin repeat and kinase containing 1 (ANKK1)/dopamine (D2) receptor gene cluster, we identified haplotype block structures in 270 Black and 368 White (n = 638) participants, from the Baltimore Epidemiologic Catchment Area cohort study, spanning the TTC12 and ANKK1 genes consisting of three SNPs (rs2303380-rs4938015-rs11604671). Informative haplotypes were examined for sex-specific associations with daily tobacco smoking initiation and cessation using longitudinal data from 1993-1994 and 2004-2005 interviews.
There was a Haplotype x Sex interaction such that Black men possessing the GTG haplotype who were smokers in 1993-2004 were more likely to have stopped smoking by 2004-2005 (55.6% GTG vs. 22.0% other haplotypes), while Black women were less likely to have quit smoking if they possessed the GTG (20.8%) versus other haplotypes (24.0%; p = .028). In Whites, the GTG haplotype (vs. other haplotypes) was associated with lifetime history of daily smoking (smoking initiation; odds ratio = 1.6; 95% CI = 1.1-2.4; p = .013). Moreover, there was a Haplotype x Sex interaction such that there was higher prevalence of smoking initiation with GTG (77.6%) versus other haplotypes (57.0%; p = .043).
In 2 different ethnic American populations, we observed man-woman variation in the influence of the rs2303380-rs4938015-rs11604671 GTG haplotype on smoking initiation and cessation. These results should be replicated in larger cohorts to establish the relationship among the rs2303380-rs4938015-rs11604671 haplotype block, sex, and smoking behavior.
11q23.1 基因组区域与黑人和白种美国人的尼古丁依赖有关。
通过对 tetratricopeptide repeat domain 12（TTC12）/ankyrin repeat 和 kinase containing 1（ANKK1）/dopamine（D2）受体基因簇内 7 个有信息的单核苷酸多态性（SNP）进行连锁不平衡分析，我们在 270 名黑人和 368 名白人（n=638）参与者中确定了 TTC12 和 ANKK1 基因的单倍型块结构，这些参与者来自巴尔的摩流行病学捕获区队列研究，由三个 SNP（rs2303380-rs4938015-rs11604671）组成。使用 1993-1994 年和 2004-2005 年访谈的纵向数据，检查有信息的单倍型与男性和女性每日吸烟起始和停止的性别特异性关联。
存在单倍型 x 性别相互作用，即 1993-2004 年吸烟的黑人男性，如果携带 GTG 单倍型，更有可能在 2004-2005 年戒烟（55.6% GTG 与 22.0% 其他单倍型），而携带 GTG 的黑人女性则不太可能戒烟（20.8% 与其他单倍型；p=0.028）。在白人中，GTG 单倍型（与其他单倍型相比）与终生每日吸烟史（吸烟起始；优势比=1.6；95%置信区间=1.1-2.4；p=0.013）相关。此外，存在单倍型 x 性别相互作用，即携带 GTG 的人比携带其他单倍型的人更有可能开始吸烟（77.6% 与其他单倍型；57.0%；p=0.043）。
在 2 个不同的美国种族人群中，我们观察到 rs2303380-rs4938015-rs11604671 GTG 单倍型对吸烟起始和停止的影响存在男女差异。应该在更大的队列中复制这些结果，以确定 rs2303380-rs4938015-rs11604671 单倍型块、性别和吸烟行为之间的关系。
