Polymorphisms in <i>HTR2A</i> and <i>DRD4</i> Predispose to Smoking and Smoking Quantity

<div><p>Background</p><p>Genes encoding the receptors involved in the dopaminergic and serotonergic pathways are potential candidates in the mechanisms of nicotine addiction.</p><p>Aims</p><p>To identify genetic variants in the promoter regions and exons of the <i>DRD4</i> and <i>HTR2A</i> genes associated with tobacco smoking and the degree of nicotine addiction in Mexican mestizos.</p><p>Methods</p><p>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 <i>DRD4</i> and <i>HTR2A</i> genes, respectively.</p><p>Results</p><p>The C allele of rs1800955 in <i>DRD4</i> was found to be associated with cigarette smoking in the HS <i>vs</i>. NS and LS <i>vs</i>. 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).</p><p>The T allele of rs6313 in <i>HTR2A</i> 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 <i>vs</i>. 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).</p><p>Conclusions</p><p>Among Mexican mestizos, the C allele of rs1800955 in the <i>DRD4</i> gene and the A allele of rs6311 in the <i>HTR2A</i> gene are associated with cigarette smoking, whereas the T allele of rs6313 in <i>HTR2A</i> is associated with cigarette smoking and the degree of nicotine addiction.</p></div

Haplotypes for <i>DRD4</i> and <i>HTR2A</i> in each comparison of the study groups.

<p>Show values of r squared in diamond. HS, Heavy smokers; LS, Light smokers; NS, Non-smokers.</p

Frequencies for minor allele in each study group and International HapMap Project population data.

<p>Frequencies for minor allele in each study group and International HapMap Project population data.</p

SNPs and associated alleles in the LS <i>vs</i>. NS and HS <i>vs</i>. NS comparisons.

<p>SNPs and associated alleles in the LS <i>vs</i>. NS and HS <i>vs</i>. NS comparisons.</p

Demographic data of the population included in the study.

<p>Demographic data of the population included in the study.</p

Associated genotypes in genes <i>DRD4</i> y <i>HTR2A</i>.

<p>Associated genotypes in genes <i>DRD4</i> y <i>HTR2A</i>.</p