Open AccessPolymorphisms in HTR2A and DRD4 Predispose to Smoking and Smoking Quantity
Author(s) -
Gloría Pérez-Rubio,
Alejandra RamírezVenegas,
Valeri Noé Díaz,
Leonor García Gómez,
Karina Elvira Fabián,
Salvador García Carmona,
Luis Alberto López-Flores,
Enrique Ambrocio-Ortiz,
Rocío Contreras Romero,
Noé Alcantar-Ayala,
Raúl H Sansores,
Ramcés FalfánValencia
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0170019
Subject(s) - genotype , allele , single nucleotide polymorphism , genotyping , nicotine , genetics , medicine , biology , gene
Background Genes encoding the receptors involved in the dopaminergic and serotonergic pathways are potential candidates in the mechanisms of nicotine addiction. Aims 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. Methods 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. Results 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). Conclusions 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.