Analysis of the Relationship Between CHRNA3/5 and EPHX1 Polymorphisms to Tobacco Intake and Development of Chronic Obstructive Pulmonary Disease (COPD)

<b>Background:</b> Chronic obstructive pulmonary disease (COPD) is a complex condition influenced by both environmental and genetic factors. Among the genetic determinants, polymorphisms in the <i>CHRNA3/5</i> and <i>EPHX1</i> genes have been implicated in nicotine dependence and susceptibility to COPD in several populations. However, evidence remains limited in admixed populations such as Brazilians. <b>Methods:</b> This cross-sectional study investigated the association between <i>CHRNA3</i> (rs1051730, rs8034191) and <i>EPHX1</i> (rs2234922) polymorphisms with tobacco nicotine dependence and COPD in a Brazilian cohort. Genotyping was performed using TaqMan^® SNP assays, and pulmonary function was assessed via spirometry according to ATS/ERS standards. Associations between genetic variants, tobacco intake, and COPD status were evaluated using χ² and Fisher's exact tests, with odds ratios (ORs) and 95% confidence intervals (CIs). Post hoc power analyses were conducted to estimate detectable effect sizes. <b>Results:</b> A total of 123 active or former smokers were analyzed. The <i>CHRNA3</i> variants (rs1051730 and rs8034191) showed a trend toward higher prevalence among individuals with heavy tobacco intake (>40 pack-years), though no significant allelic or genotypic differences were found between COPD and control groups (<i>p</i> > 0.05). The <i>EPHX1</i> rs2234922 A allele was significantly more frequent in COPD patients, suggesting increased disease risk (<i>p</i> < 0.05), while the GG genotype appeared protective. Post hoc power analyses indicated moderate power (≈0.56-0.63) for the observed associations. <b>Conclusions:</b> In this Brazilian population, the <i>CHRNA3/5</i> polymorphisms may influence nicotine dependence, while <i>EPHX1</i> rs2234922 appears to be associated with COPD susceptibility. These findings support a potential genetic contribution to disease risk and tobacco nicotine dependence, warranting further large-scale studies to confirm these associations and explore their therapeutic implications.