Department of Pathology, School of Medicine, Yale University, New Haven, CT, 06511, USA.
Hum Genet. 2014 Mar;133(3):357-65. doi: 10.1007/s00439-013-1388-y. Epub 2013 Nov 1.
Positive genetic associations of rs6313 (102T/C at exon 1) and rs6311 (-1438A/G) on the 5-hydroxytryptamine (serotonin) 2A receptor gene (HTR2A or 5-HT2A) were reported for alcohol and drug abuse; however, other association studies failed to produce consistent results supporting the susceptibility of the two single nucleotide polymorphisms (SNPs). To clarify the associations of the HTR2A gene with substance use disorders, we performed a meta-analysis based on the genotypes from the available candidate gene association studies of the two SNPs with alcohol and drug abuse from multiple populations. Evidence of association was found for HTR2A rs6313 in all the combined studies (e.g., allelic P = 0.0048 and OR 0.86, 95 % CI 0.77-0.95) and also in the combined studies of alcohol dependence (abuse) (e.g., allelic P = 0.0001 and OR 0.71, 95 % CI 0.59-0.85). The same association trend was also observed in the Study of Addiction: Genetics and Environment datasets. The meta-analysis supports a contribution of the HTR2A gene to the susceptibility to substance use disorders, particularly alcohol dependence.
先前有研究报道,5-羟色胺(血清素)2A 受体基因(HTR2A 或 5-HT2A)上 rs6313(外显子 1 的 102T/C)和 rs6311(-1438A/G)与酒精和药物滥用存在正相关,但其他关联研究未能得出一致的结果来支持这两个单核苷酸多态性(SNP)与易感性的相关性。为了阐明 HTR2A 基因与物质使用障碍的关联,我们基于来自多个群体的这两个 SNP 与酒精和药物滥用的候选基因关联研究的基因型进行了荟萃分析。在所有的综合研究中都发现了 HTR2A rs6313 与物质使用障碍有关联的证据(例如,等位基因 P = 0.0048 和 OR 0.86,95%CI 0.77-0.95),并且在酒精依赖(滥用)的综合研究中也存在关联(例如,等位基因 P = 0.0001 和 OR 0.71,95%CI 0.59-0.85)。成瘾研究:遗传学和环境数据集也观察到了相同的关联趋势。荟萃分析支持 HTR2A 基因对物质使用障碍易感性的贡献,特别是对酒精依赖的易感性。