Association of metabotropic glutamate receptor 7 gene with nicotine dependence in a Chinese Han population: A cross-sectional candidate-gene association study.

IF 2.4 4区医学 Q2 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH

Tobacco Induced Diseases Pub Date : 2026-08-01 eCollection Date: 2026-01-01 DOI:10.18332/tid/219820

Jinjie Zhao, Mengying Li, Ruibo Wang, Wenjing Shen, Meng Li

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引用次数: 0

Abstract

Introduction: Despite a global decline in prevalence, cigarette smoking remains a significant public health issue. Tobacco addiction is principally caused by nicotine dependence (ND). This study aimed to investigate the relationship between the metabotropic glutamate receptor 7 (GRM7) gene and ND in Chinese adults.

Methods: This two-stage, cross-sectional, candidate-gene association study first enrolled a discovery cohort of 1609 participants from Kunming, Yunnan, China (2017-2019), followed by a replication stage involving 1329 individuals from Jincheng and Taiyuan, Shanxi, China (2012-2013). Association analysis between the GRM7 gene and ND was performed at individual SNP, haplotype, and whole-gene levels. Logistic and linear regression models were employed for single-SNP association analyses. Heaviness of smoking index (HSI) and Fagerström test for nicotine dependence (FTND) were used to assess ND.

Results: Rs77452956, rs74791991, and rs2176404 were significantly associated with ND proxied by HSI, with p-values of <0.001, 0.001, and 0.002, respectively. In the replication analysis, rs74791991 and rs2176404 showed associations with ND (p=0.006 and 0.082, respectively), while rs77452956 was linked to smoking status (p=0.014). Haplotype-based association analysis revealed that two haplotypes, C-C-T and T-G-C, comprising rs74791991, rs111848366, and rs7633313, were associated significantly with HSI, with p<0.001 and p=0.003, respectively. Gene-based analysis also revealed a significant association between GRM7 and HSI (p=0.006). Functional assessment suggested that rs77452956 and rs74791991 have regulatory capacity. Furthermore, the derived C alleles of rs74791991, rs2176404, and rs77452956 showed accelerated evolution.

Conclusions: We identified three SNPs, rs74791991, rs2176404, and rs77452956, associated with ND in Han Chinese individuals. Our findings suggest a potential role of GRM7 in susceptibility to smoking-related behaviors and warrant further investigation to determine its relevance in smoking cessation.

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中国汉族人群中代谢性谷氨酸受体7基因与尼古丁依赖的关联：一项横断面候选基因关联研究。

导言：尽管全球吸烟率下降，但吸烟仍然是一个重大的公共卫生问题。烟草成瘾主要是由尼古丁依赖引起的。本研究旨在探讨中国成人代谢性谷氨酸受体7 （GRM7）基因与ND的关系。方法：这项两阶段、横断面、候选基因关联研究首先招募了来自中国云南昆明的1609名参与者（2017-2019），然后招募了来自中国山西晋城和太原的1329名参与者（2012-2013）。在单个SNP、单倍型和全基因水平上进行GRM7基因与ND之间的关联分析。单snp关联分析采用Logistic和线性回归模型。使用吸烟重度指数（HSI）和Fagerström尼古丁依赖试验（FTND）评估ND。结果：Rs77452956、rs74791991和rs2176404与HSI代理ND有显著相关性，GRM7和HSI的p值均为p=0.006。功能评价提示rs77452956和rs74791991具有调控能力。此外，衍生的C等位基因rs74791991、rs2176404和rs77452956的进化速度加快。结论：我们鉴定出3个snp位点rs74791991、rs2176404和rs77452956与汉族ND相关。我们的研究结果表明GRM7在吸烟相关行为易感性中的潜在作用，值得进一步研究以确定其与戒烟的相关性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Tobacco Induced Diseases SUBSTANCE ABUSE-PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH

CiteScore

5.30

自引率

5.40%

发文量

审稿时长

12 weeks

期刊介绍： Tobacco Induced Diseases encompasses all aspects of research related to the prevention and control of tobacco use at a global level. Preventing diseases attributable to tobacco is only one aspect of the journal, whose overall scope is to provide a forum for the publication of research articles that can contribute to reducing the burden of tobacco induced diseases globally. To address this epidemic we believe that there must be an avenue for the publication of research/policy activities on tobacco control initiatives that may be very important at a regional and national level. This approach provides a very important "hands on" service to the tobacco control community at a global scale - as common problems have common solutions. Hence, we see ourselves as "connectors" within this global community. The journal hence encourages the submission of articles from all medical, biological and psychosocial disciplines, ranging from medical and dental clinicians, through health professionals to basic biomedical and clinical scientists.