title: Polymorphisms in HTR2A and DRD4 Predispose to Smoking and Smoking Quantity.
abstract: BACKGROUND
  Genes encoding the receptors involved in the dopaminergic and serotonergic pathways are potential candidates in the mechanisms of nicotine addiction.
  
  
  OBJECTIVE
  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.
authors.affiliation: Laboratorio HLA, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, México City, México.
authors.forename: Gloria
authors.initials: G
authors.lastname: Pérez-Rubio
authors.affiliation: Departamento de Investigación en Tabaquismo y EPOC, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, México City, México.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Ramírez-Venegas
authors.affiliation: Departamento de Investigación en Tabaquismo y EPOC, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, México City, México.
authors.forename: Valeri
authors.initials: V
authors.lastname: Noé Díaz
authors.affiliation: Departamento de Investigación en Tabaquismo y EPOC, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, México City, México.
authors.forename: Leonor
authors.initials: L
authors.lastname: García Gómez
authors.affiliation: Laboratorio HLA, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, México City, México.
authors.forename: Karina
authors.initials: K
authors.lastname: Elvira Fabián
authors.affiliation: Laboratorio HLA, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, México City, México.
authors.forename: Salvador
authors.initials: S
authors.lastname: García Carmona
authors.affiliation: Laboratorio HLA, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, México City, México.
authors.forename: Luis A
authors.initials: LA
authors.lastname: López-Flores
authors.affiliation: Laboratorio HLA, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, México City, México.
authors.forename: Enrique
authors.initials: E
authors.lastname: Ambrocio-Ortiz
authors.affiliation: Departamento de Investigación en Tabaquismo y EPOC, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, México City, México.
authors.forename: Rocío
authors.initials: R
authors.lastname: Contreras Romero
authors.affiliation: Banco de sangre, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, México City, México.
authors.forename: Noé
authors.initials: N
authors.lastname: Alcantar-Ayala
authors.affiliation: Departamento de Investigación en Tabaquismo y EPOC, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, México City, México.
authors.forename: Raúl H
authors.initials: RH
authors.lastname: Sansores
authors.affiliation: Laboratorio HLA, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, México City, México.
authors.forename: Ramcés
authors.identifier: http://orcid.org/0000-0001-6877-8124
authors.initials: R
authors.lastname: Falfán-Valencia
mesh_terms: D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics* / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D012907:Smoking / Q000453:epidemiology / Q000235:genetics*
chemical_list: C493599:DRD4 protein, human; D044402:Receptor, Serotonin, 5-HT2A; D050638:Receptors, Dopamine D4