Polymorphisms in HTR2A and DRD4 Predispose to Smoking and Smoking Quantity

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...

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Published in:	PloS one Vol. 12; no. 1; p. e0170019
Main Authors:	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
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 19-01-2017 Public Library of Science (PLoS)
Subjects:	Addictions Aged Alleles Biology and Life Sciences Case-Control Studies Cigarette smoking Cigarettes Compounds Cross-Sectional Studies Deoxyribonucleic acid Disease DNA DNA methylation Dopamine Dopamine D4 receptors Dopamine receptors Exons Genes Genetic aspects Genetic Association Studies Genetic diversity Genetic variance Genotyping Haplotypes Health aspects Humans Male Medicine and Health Sciences Mexico - epidemiology Middle Aged Nicotine People and Places Polymorphism, Single Nucleotide - genetics Polymorphism, Single Nucleotide - physiology Population Public health Real-Time Polymerase Chain Reaction Receptor, Serotonin, 5-HT2A - genetics Receptors Receptors, Dopamine D4 - genetics Serotonin Single nucleotide polymorphisms Single-nucleotide polymorphism Smokers Smoking Smoking - epidemiology Smoking - genetics Smoking cessation Social Sciences Studies Tobacco Tobacco smoking California
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceptualization: GPR ARV RHS RFV.Data curation: GPR RFV.Formal analysis: GPR ARV RHS RFV.Funding acquisition: ARV RHS RFV.Investigation: GPR ARV VND LGG EAO LALF RCR KEF SGC NAA RHS RFV.Methodology: GPR ARV VND LGG RCR KEF SGC NAA EAO LALF RHS RFV.Project administration: GPR ARV RHS RFV.Resources: ARV VND LGG EAO LALF RCR KEF SGC NAA.Software: GPR KEF SGC EAO LALF.Supervision: GPR ARV RHS RFV.Validation: GPR VND LGG LALF RHS RFV.Visualization: GPR ARV VND LGG RCR KEF SGC NAA EAO LALF RHS RFV.Writing – original draft: GPR ARV RHS RFV.Writing – review & editing: GPR ARV EAO LALF RHS RFV. Competing Interests: The authors have declared that no competing interests exist.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0170019