Pérez-Rubio Gloria, Pérez-Rodríguez Martha E, Fernández-López Juan Carlos, Ramírez-Venegas Alejandra, García-Colunga Jesús, Ávila-Moreno Federico, Camarena Angel, Sansores Raúl H, Falfán-Valencia Ramcés
Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Laboratorio HLA, México, DF, México.
Instituto Mexicano del Seguro Social., Unidad de Investigación Médica en Inmunología, CMN S-XXI, México, DF, México.
Pharmacogenomics. 2016 Jul;17(10):1145-1158. doi: 10.2217/pgs-2016-0020. Epub 2016 Jun 29.
To identify genetic variants associated with greater tobacco consumption in a Mexican population.
PATIENTS & METHODS: Daily smokers were classified as light smokers (LS; n = 742), heavy smokers (HS; n = 601) and nonsmokers (NS; n = 606). In the first stage, a genotyping microarray that included 347 SNPs in CHRNA2-CHRNA7/CHRNA10, CHRNB2-CHRNB4 and NRXN1 genes and 37 ancestry-informative markers was used to analyze 707 samples (187 HS, 328 LS and 192 NS). In the second stage, 14 SNPs from stage 1 were validated in the remaining samples (HS, LS and NS; n = 414 in each group) using real-time PCR. To predict the role of the associated SNPs, an in silico analysis was performed.
Two SNPs in NRXN1 and two in CHRNA5 were associated with cigarette consumption, while rs10865246/C (NRXN1) was associated with high nicotine addiction. The in silico analysis revealed that rs1882296/T had a high level of homology with Hsa-miR-6740-5p, which encodes a putative miRNA that targets glutamate receptor subunits (GRIA2, GRID2) and GABA receptor subunits (GABRG1, GABRA4, GABRB2), while rs1882296/C had a high level of homology with Hsa-miR-6866-5p, which encodes a different miRNA that targets GRID2 and GABRB2.
In a Mexican Mestizo population, greater consumption of cigarettes was influenced by polymorphisms in the NRXN1 and CHRNA5 genes. We proposed new hypotheses regarding the putative roles of miRNAs that influence the GABAergic and glutamatergic pathways in smoking addiction.
在墨西哥人群中鉴定与更高烟草消费量相关的基因变异。
每日吸烟者被分为轻度吸烟者（LS；n = 742）、重度吸烟者（HS；n = 601）和不吸烟者（NS；n = 606）。在第一阶段，使用包含CHRNA2-CHRNA7/CHRNA10、CHRNB2-CHRNB4和NRXN1基因中的347个单核苷酸多态性（SNP）以及37个祖先信息标记的基因分型微阵列分析707个样本（187名重度吸烟者、328名轻度吸烟者和192名不吸烟者）。在第二阶段，使用实时聚合酶链反应在其余样本（重度吸烟者、轻度吸烟者和不吸烟者；每组n = 414）中验证来自第一阶段的14个SNP。为预测相关SNP的作用，进行了计算机模拟分析。
NRXN1基因中的两个SNP和CHRNA5基因中的两个SNP与卷烟消费相关，而rs10865246/C（NRXN1）与高尼古丁成瘾相关。计算机模拟分析显示，rs1882296/T与Hsa-miR-6740-5p具有高度同源性，Hsa-miR-6740-5p编码一种假定的微小RNA，其靶向谷氨酸受体亚基（GRIA2、GRID2）和γ-氨基丁酸受体亚基（GABRG1、GABRA4、GABRB2），而rs1882296/C与Hsa-miR-6866-5p具有高度同源性，Hsa-miR-6866-5p编码一种不同的微小RNA，其靶向GRID2和GABRB2。
在墨西哥梅斯蒂索人群中，更高的卷烟消费量受NRXN1和CHRNA5基因多态性的影响。我们提出了关于影响吸烟成瘾中γ-氨基丁酸能和谷氨酸能途径的微小RNA假定作用的新假设。
