SLC6A4 STin2 VNTR genetic polymorphism is associated with tobacco use disorder, but not with successful smoking cessation or smoking characteristics: a case control study
SLC6A4 STin2 VNTR genetic polymorphism is associated with tobacco use disorder, but not with successful smoking cessation or smoking characteristics: a case control study
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DOI：
10.1186/1471-2156-15-78
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发表时间：
2014-06-27
期刊：
影响因子：
2.9
通讯作者：
Vargas Nunes, Sandra Odebrecht
中科院分区：
文献类型：
--
作者：
Pizzo de Castro, Marcia Regina;Maes, Michael;Vargas Nunes, Sandra Odebrecht
背景：本研究的目的是确定血清素转运蛋白 (SLC6A4) 基因第二个内含子 (STin2) 中可变数量的串联重复序列 (VNTR) 是否与烟草使用障碍、成功戒烟或吸烟特征相关。在这项病例对照研究中，招募了根据 DSM IV 标准诊断的当前吸烟障碍患者 (n = 185) 和根据 CDC 标准诊断的从不吸烟者 (n = 175)，并接受了 52 周的联合药物治疗和认知治疗。成功戒烟定义为呼出一氧化碳< 6 ppm。使用基于多重 PCR 的方法评估 SLC6A4 基因 STin2 VNTR 多态性。在基线时，使用 Fagerstr m 尼古丁依赖性测试 (FTND) 和 ASSIST 量表对参与者进行评估。结果：STin2.12 等位基因（OR = 2.45；95% CI = 1.44-4.15，p < 0.001）与烟草使用障碍风险增加相关，而 STin2.10/10 基因型（OR = 0.42；95% CI）与烟草使用障碍风险增加相关。 0.25-0.71，p < 0.001）风险降低。烟草使用障碍与 STin2.10 或 STin2.9 等位基因或其他基因型（STin2.12/12、12/10、12/9、10/9 或 9/9）之间没有显着关联。 STin2 基因型和等位基因与成功戒烟、吸烟特征和酒精或镇静剂使用风险增加之间没有显着关联。结论：我们的结果表明 STin2.10/10 基因型和 STin2.12 等位基因与烟草使用障碍或尼古丁依赖相关，但与治疗反应或依赖严重程度无关。据推测，ST2in。 12等位基因通过调节血清素代谢可能参与烟草使用障碍或尼古丁依赖的病理生理学。
Background: The aim of this study was to determine if variable number of tandem repeats (VNTR) in the second intron (STin2) of the serotonin transporter (SLC6A4) gene was associated with tobacco use disorder, successful smoking cessation, or smoking characteristics. In this case-control study, patients with current tobacco use disorder, diagnosed according to DSM IV criteria (n = 185), and never-smokers, diagnosed according to CDC criteria (n = 175), were recruited and received 52 weeks of combined pharmacotherapy and cognitive therapy. Successful smoking cessation was defined as exhaled carbon monoxide < 6 ppm. SLC6A4 gene STin2 VNTR polymorphism was assessed using a Multiplex-PCR-based method. At baseline, participants were evaluated using the Fagerstr m Test for Nicotine Dependence (FTND) and the ASSIST scale.Results: The STin2.12 allele (OR = 2.45; 95% CI = 1.44-4.15, p < 0.001) was associated with an increased risk for tobacco use disorder, while the STin2.10/10 genotype (OR = 0.42; 95% CI 0.25-0.71, p < 0.001) decreased risk. There were no significant associations between tobacco use disorder and the STin2.10 or STin2.9 alleles or the other genotypes (STin2.12/12, 12/10, 12/9, 10/9 or 9/9). There were no significant associations between the STin2 genotypes and alleles and successful smoking cessation, smoking characteristics and increased alcohol or sedative use risk.Conclusions: Our results suggest that the STin2.10/10 genotype and STin2.12 allele are associated with tobacco use disorder or nicotine dependence, but not with treatment response or severity of dependence. It is hypothesized that the ST2in. 12 allele by modulating the metabolism of serotonin may participate in the pathophysiology of tobacco use disorder or nicotine dependence.