State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, China.
ACT Center for Tobacco Treatment, Education and Research, Department of Otolaryngology and Communicative Sciences, University of Mississippi Medical Center, Jackson, MS, USA.
Sci Rep. 2017 Aug 29;7(1):9745. doi: 10.1038/s41598-017-09492-8.
Although numerous studies have revealed significant associations between variants in the nicotinic acetylcholine receptors (nAChR) subunits and nicotine dependence (ND), only few studies were performed in Chinese subjects. Here, we performed association and interaction analysis for 20 single nucleotide polymorphisms (SNPs) in the CHRNB3-CHRNA6 gene cluster with ND in a Chinese Han population (N = 5,055). We found nominally significant associations for all tested SNPs with ND measured by the Fagerström Test for Nicotine Dependence score; of these, 11 SNPs remained significant after Bonferroni correction for multiple tests (p = 9 × 10~2 × 10). Further conditional analysis indicated that no other SNP was significantly associated with ND independent of the most-highly significant SNP, rs6474414. Also, our haplotype-based association analysis indicated that each haplotype block was significantly associated with ND (p < 0.01). Further, we provide the first evidence of the genetic interaction of these two genes in affecting ND in this sample with an empirical p-value of 0.0015. Finally, our meta-analysis of samples with Asian and European origins for five SNPs in CHRNB3 showed significant associations with ND, with p-values ranging from 6.86 × 10 for rs13280604 to 6.50 × 10 for rs4950 This represents the first study showing that CHRNB3/A6 are highly associated with ND in a large Chinese Han sample.
尽管许多研究揭示了尼古丁乙酰胆碱受体（nAChR）亚单位变体与尼古丁依赖（ND）之间存在显著关联，但仅有少数研究在中国人群中进行。在此，我们对 CHRNB3-CHRNA6 基因簇中的 20 个单核苷酸多态性（SNP）与中国汉族人群 ND 之间的关联和相互作用进行了分析（N=5055）。我们发现，所有测试的 SNP 与尼古丁依赖的 Fagerström 测试评分之间存在显著关联；其中，11 个 SNP 在经过多重检验的 Bonferroni 校正后仍具有统计学意义（p=9×10~2×10）。进一步的条件分析表明，没有其他 SNP 与 ND 显著相关，独立于最显著的 SNP，rs6474414。此外，我们基于单体型的关联分析表明，每个单体型块与 ND 显著相关（p<0.01）。此外，我们首次提供了这两个基因在影响本样本 ND 方面遗传相互作用的证据，经验性 p 值为 0.0015。最后，我们对亚洲和欧洲起源的样本进行了五个 CHRNB3 中 SNP 的荟萃分析，发现它们与 ND 显著相关，p 值范围从 rs13280604 的 6.86×10 到 rs4950 的 6.50×10。这代表了第一项研究，表明 CHRNB3/A6 与中国汉族大样本中的 ND 高度相关。
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