Pérez-Rubio Gloria, Ramírez-Venegas Alejandra, Noé Díaz Valeri, García Gómez Leonor, Elvira Fabián Karina, García Carmona Salvador, López-Flores Luis A, Ambrocio-Ortiz Enrique, Contreras Romero Rocío, Alcantar-Ayala Noé, Sansores Raúl H, Falfán-Valencia Ramcés
Laboratorio HLA, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, México City, México.
Departamento de Investigación en Tabaquismo y EPOC, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, México City, México.
PLoS One. 2017 Jan 19;12(1):e0170019. doi: 10.1371/journal.pone.0170019. eCollection 2017.
Genes encoding the receptors involved in the dopaminergic and serotonergic pathways are potential candidates in the mechanisms of nicotine addiction.
To identify genetic variants in the promoter regions and exons of the DRD4 and HTR2A genes associated with tobacco smoking and the degree of nicotine addiction in Mexican mestizos.
The study included 438 non-smokers (NS) and 1,157 current smokers, ranked based on their consumption of cigarettes per day (cpd): 574 heavy smokers (HS, >20 cpd) and 583 light smokers (LS, 1-10 cpd). Genotyping was performed for 4 and 8 single nucleotide polymorphisms (SNPs) in the DRD4 and HTR2A genes, respectively.
The C allele of rs1800955 in DRD4 was found to be associated with cigarette smoking in the HS vs. NS and LS vs. NS comparisons (p = 2.34E-03 and p = 1.13E-03, respectively); the association was maintained in the homozygous CC genotype (p = 5.00E-04 and p = 2.00E-04, respectively). The T allele of rs6313 in HTR2A was significantly associated with cigarette smoking and a greater degree of nicotine addiction (p = 4.77E-03, OR = 1.55); the association was maintained in the homozygous genotype (TT) (p = 4.90E-03, OR = 1.96). The A allele of rs6313 was associated with cigarette smoking in the HS vs. NS comparison (p = 1.53E-02, OR = 1.36); the risk was nearly doubled in the homozygous AA genotype (p = 1.30E-03, OR = 1.83) compared with the heterozygous GA genotype (OR = 1.38).
Among Mexican mestizos, the C allele of rs1800955 in the DRD4 gene and the A allele of rs6311 in the HTR2A gene are associated with cigarette smoking, whereas the T allele of rs6313 in HTR2A is associated with cigarette smoking and the degree of nicotine addiction.
编码多巴胺能和血清素能途径中相关受体的基因是尼古丁成瘾机制中的潜在候选基因。
在墨西哥混血人群中，鉴定与吸烟及尼古丁成瘾程度相关的DRD4和HTR2A基因启动子区域和外显子中的基因变异。
该研究纳入了438名不吸烟者（NS）和1157名当前吸烟者，根据他们每天的香烟消费量（cpd）进行排名：574名重度吸烟者（HS，>20 cpd）和583名轻度吸烟者（LS，1 - 10 cpd）。分别对DRD4基因中的4个和HTR2A基因中的8个单核苷酸多态性（SNP）进行基因分型。
在重度吸烟者与不吸烟者以及轻度吸烟者与不吸烟者的比较中，发现DRD4基因中rs1800955的C等位基因与吸烟有关（分别为p = 2.34E - 03和p = 1.13E - 03）；在纯合CC基因型中该关联依然存在（分别为p = 5.00E - 04和p = 2.00E - 04）。HTR2A基因中rs6313的T等位基因与吸烟及更高程度的尼古丁成瘾显著相关（p = 4.77E - 03，OR = 1.55）；在纯合基因型（TT）中该关联依然存在（p = 4.90E - 03，OR = 1.96）。在重度吸烟者与不吸烟者的比较中，rs6313的A等位基因与吸烟有关（p = 1.53E - 02，OR = 1.36）；与杂合GA基因型（OR = 1.38）相比，纯合AA基因型的风险几乎翻倍（p = 1.30E - 03，OR = 1.83）。
在墨西哥混血人群中，DRD4基因中rs1800955的C等位基因和HTR2A基因中rs6311的A等位基因与吸烟有关，而HTR2A基因中rs6313的T等位基因与吸烟及尼古丁成瘾程度有关。
