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

TL;DR

This study explores how genetic variations in CHRNA3/5 and EPHX1 genes relate to smoking habits and COPD risk in a Brazilian population.

Contribution

The study identifies potential associations between EPHX1 rs2234922 and COPD risk in an admixed Brazilian cohort.

Findings

CHRNA3 variants showed a trend toward higher prevalence in heavy smokers but no significant COPD association.

The EPHX1 rs2234922 A allele was significantly more frequent in COPD patients, suggesting increased risk.

Post hoc power analyses indicated moderate statistical power for observed associations.

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a complex condition influenced by both environmental and genetic factors. Among the genetic determinants, polymorphisms in the CHRNA3/5 and EPHX1 genes have been implicated in nicotine dependence and susceptibility to COPD in several populations. However, evidence remains limited in admixed populations such as Brazilians. Methods: This cross-sectional study investigated the association between CHRNA3 (rs1051730, rs8034191) and EPHX1 (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. Results: A total of 123 active or former smokers were analyzed. The CHRNA3 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 (p > 0.05). The EPHX1 rs2234922 A allele was significantly more frequent in COPD patients, suggesting increased disease risk (p < 0.05), while the GG genotype appeared protective. Post hoc power analyses indicated moderate power (≈0.56–0.63) for the observed associations. Conclusions: In this Brazilian population, the CHRNA3/5 polymorphisms may influence nicotine dependence, while EPHX1 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.

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