Pérez-Rubio Gloria, López-Flores Luis Alberto, Ramírez-Venegas Alejandra, Noé-Díaz Valeri, García-Gómez Leonor, Ambrocio-Ortiz Enrique, Sánchez-Romero Candelaria, Hernández-Zenteno Rafael De Jesús, Sansores Raúl Humberto, Falfán-Valencia Ramcés
Laboratorio HLA, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
Departamento de Investigación en Tabaquismo y EPOC, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
Gene. 2017 Sep 10;628:205-210. doi: 10.1016/j.gene.2017.07.051. Epub 2017 Jul 20.
Nicotine is the main component of cigarettes that causes addiction, which is considered a complex disease, and genetic factors have been proposed to be involved in the development of addiction. The CYP2A6 gene encodes the main enzyme responsible for nicotine metabolism. Depending on the study population, different genetic variants of CYP2A6 associated with cigarette smoking have been described. Therefore, we evaluated the possible association between SNPs in CYP2A6 with cigarette smoking and nicotine addiction-related variables in Mexican mestizo smokers. We performed a genetic association study comparing light smokers (LS, n=349), heavy smokers (HS, n=351) and never-smokers (NS, n=394). SNPs rs1137115, rs4105144, rs1801272 and rs28399433 were genotyped in the CYP2A6 gene. We found that the A allele of rs1137115 (OR=1.41) in exon 1 of CYP2A6 and the T allele of rs4105144 (OR=1.32) in the 5' UTR of the gene are associated with the risk of cigarette smoking (p<0.05); rs1137115 affects the level of alternative splicing, resulting in a CYP2A6 isoform with low enzymatic activity, whereas rs4105144 is likely to be in a binding site for the transcription factor for glucocorticoids receptor (GR) and regulates the expression of CYP2A6. In addition, having a greater number of risk alleles (rs1137115 (A), rs4105144 (T) and rs28399433 (G)) is associated with a younger age at onset. The present study shows that in Mexican mestizos, the analyzed SNPs confer greater risk in terms of consumption and age of onset.
尼古丁是香烟中导致成瘾的主要成分，成瘾被认为是一种复杂的疾病，并且有研究提出遗传因素参与成瘾的发展过程。CYP2A6基因编码负责尼古丁代谢的主要酶。根据研究人群的不同，已描述了与吸烟相关的CYP2A6的不同基因变体。因此，我们评估了墨西哥混血吸烟者中CYP2A6基因单核苷酸多态性（SNPs）与吸烟及尼古丁成瘾相关变量之间的可能关联。我们进行了一项遗传关联研究，比较了轻度吸烟者（LS，n = 349）、重度吸烟者（HS，n = 351）和从不吸烟者（NS，n = 394）。对CYP2A6基因中的rs1137115、rs4105144、rs1801272和rs28399433这几个SNPs进行了基因分型。我们发现，CYP2A6基因外显子1中rs1137115的A等位基因（OR = 1.41）以及该基因5'非翻译区中rs4105144的T等位基因（OR = 1.32）与吸烟风险相关（p < 0.05）；rs1137115影响可变剪接水平，导致产生一种酶活性低的CYP2A6同工型，而rs4105144可能位于糖皮质激素受体（GR）转录因子的结合位点，并调节CYP2A6的表达。此外，拥有更多风险等位基因（rs1137115（A）、rs4105144（T）和rs28399433（G））与发病年龄较小相关。本研究表明，在墨西哥混血人群中，所分析的SNPs在吸烟量和发病年龄方面带来了更大风险。
