| Summary: | Cigarette smoking is influenced by nicotine’s effects on dopaminergic activity, which appear to be moderated by genetic variation, particularly a variable number tandem repeat (VNTR, 48 bp) polymorphism in the third exon of the dopamine receptor gene (<i>DRD4</i>). Smokers with the VNTR ≥7 repeats (long, L allele) report markedly increased participation in some smoking behaviors; hence, our aim was to evaluate the association of the L allele in Mexican Mestizo smokers with and without COPD. The <i>DRD4</i> VNTR 48 bp was genotyped in 492 Mexican Mestizo smokers: 164 COPD patients (≥20 cigarettes per day, cpd), 164 heavy smokers without COPD (HS, ≥20 cpd) and 164 light smokers without COPD (LS, 1−10 cpd). In the dominant model analysis (SL + LL vs. SS), men in the COPD and HS groups showed a statistical difference compared to LS (<i>p</i> = 0.01, OR = 2.06, CI 95% 1.17−3.64 and <i>p</i> = 0.05, OR = 1.88, CI 95% 1.03−3.45, respectively). In addition, by clustering smokers >20 cpd (COPD + HS) and comparing with the LS group, we found an association with increased risk of higher tobacco smoking <i>p</i> = 0.01, OR = 1.99, CI 95% 1.18−3.34. In conclusion, the long allele (L) in the VNTR of the <i>DRD4</i> gene is associated with the risk of presenting higher tobacco smoking in male Mexican Mestizo smokers.
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