苦味受体基因 TAS2R38 的遗传变异与汉族吸烟者的吸烟行为有关。
Genetic variations in the bitter taste receptor gene TAS2R38 are related to cigarette smoking behavior in Han Chinese smokers.
机构信息
Joint Institute of Tobacco and Health, Kunming, 650106, Yunnan, China.
Medical Faculty, Kunming University of Science and Technology, Kunming, 650500, China.
出版信息
Genes Genomics. 2022 Nov;44(11):1363-1374. doi: 10.1007/s13258-022-01311-3. Epub 2022 Sep 20.
BACKGROUND
Smoking behavior is influenced by multiple genes, including the bitter taste gene TAS2R38. It has been reported that the correlation between TAS2R38 and smoking behavior has ethnicity-based differences. However, the TAS2R38 status in Chinese smokers is still unclear.
OBJECTIVE
This study aims to investigate the possible relationship between genetic variations in TAS2R38 (A49P, V262A and I296V) and smoking behaviors in the Han Chinese population.
METHODS
The haplotype analyses were performed and smoking behavior questionnaire was completed by 1271 individuals. Genetic association analyses for smoking behavior were analyzed using chi-square test. Further, for investigating the molecular mechanism of TAS2R38 variants effect on smoking behavior, we conducted TAS2R38-PAV and TAS2R38-AVI expression plasmids and tested the cellular calcium assay by cigarette smoke compounds stimulus in HEK293.
RESULTS
Significant associations of genetic variants within TAS2R38 were identified with smoking behavior. We found a higher PAV/PAV frequency than AVI/AVI in moderate and high nicotine dependence (FTND ≥ 4; X = 4.611, 1 df, p = 0.032) and strong cigarette smoke flavor intensity preference (X = 4.5383, 1 df, p = 0.033) in participants. Furthermore, in the in vitro cellular calcium assay, total particle matter (TPM), N-formylnornicotine and cotinine, existing in cigarette smoke, activated TAS2R38-PAV but not TAS2R38-AVI-transfected cells.
CONCLUSION
Our data highlights that genetic variations in TAS2R38 are related to smoking behavior, especially nicotine dependence and cigarette smoke flavor intensity preference. Our findings may encourage further consideration of the taste process to identify individuals susceptible to nicotine dependence, particularly Han Chinese smokers.
背景
吸烟行为受多个基因的影响,包括苦味基因 TAS2R38。已有报道称,TAS2R38 与吸烟行为的相关性存在种族差异。然而,中国吸烟者的 TAS2R38 状况尚不清楚。
目的
本研究旨在探讨 TAS2R38(A49P、V262A 和 I296V)基因变异与汉族人群吸烟行为之间的可能关系。
方法
对 1271 名个体进行了单倍型分析和吸烟行为问卷调查。采用卡方检验分析吸烟行为的遗传关联。此外,为了研究 TAS2R38 变异对吸烟行为影响的分子机制,我们构建了 TAS2R38-PAV 和 TAS2R38-AVI 表达质粒,并在 HEK293 细胞中用香烟烟雾化合物刺激进行了细胞钙测定。
结果
TAS2R38 内的遗传变异与吸烟行为存在显著关联。我们发现,在中度和高度尼古丁依赖(FTND≥4;X=4.611,1 df,p=0.032)和强烈的香烟烟雾味道强度偏好(X=4.5383,1 df,p=0.033)的参与者中,PAV/PAV 频率高于 AVI/AVI。此外,在体外细胞钙测定中,总颗粒物(TPM)、N-甲酰基降烟碱和可替宁等存在于香烟烟雾中的物质激活了 TAS2R38-PAV 转染细胞,但不激活 TAS2R38-AVI 转染细胞。
结论
我们的数据表明,TAS2R38 中的遗传变异与吸烟行为有关,特别是尼古丁依赖和香烟烟雾味道强度偏好。我们的发现可能鼓励进一步考虑味觉过程,以识别易患尼古丁依赖的个体,特别是汉族吸烟者。