Abstract
Genetic variability influences the susceptibility to and severity of complex diseases; there is a lower risk of COPD in Hispanics than in non-Hispanic Caucasians. In this study, we included 830 Mexican-Mestizo subjects; 299 were patients with COPD secondary to tobacco smoking, and 531 were smokers without COPD. We employed a customized genotyping array of single nucleotide polymorphisms (SNPs). The population structure was evaluated by principal component analysis and allele association through a logistic regression model and haplotype identification. In this study, 118 individuals were identified with a high Caucasian component and 712 with a high Amerindian component. Independent of the ancestral contribution, two SNPs were associated with a reduced risk (p ≤ 0.01) of developing COPD in the CYP2A6 (rs4105144) and CYP2B6 (rs10426235) genes; however, a haplotype was associated with an increased risk of COPD (p = 0.007, OR = 2.47) in the CHRNA5-CHRNA3 loci among smokers with a high Caucasian component. In Mexican-Mestizo smokers, there are SNPs in genes that encode proteins responsible for the metabolism of nicotine associated with a lower risk of COPD; individuals with a high Caucasian component harboring a haplotype in the CHRNA5-CHRNA3 loci have a higher risk of suffering from COPD.
Highlights
Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable condition characterized by dyspnea, chronic cough, and airflow limitation produced by airway or alveolar abnormalities, usually triggered by prolonged exposure to harmful particles or gases
With a high AME contribution, we found that single nucleotide polymorphisms (SNPs) in the CYP2B6 and CYP2A6 genes were associated with a lower risk of suffering COPD; of these two polymorphisms, the best studied is CYP2A6, which codes for the main hepatic enzyme metabolizing nicotine and cotinine [22]
Our results provide evidence that COPD is a complex disease in which environmental factors are involved; genetic factors located on chromosome 19 are essential and contribute to COPD
Summary
Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable condition characterized by dyspnea, chronic cough, and airflow limitation produced by airway or alveolar abnormalities, usually triggered by prolonged exposure to harmful particles or gases. The most common but not the only risk factor is tobacco smoking [1]. This disease results from the complex interaction among chronic tobacco smoking, airway hypersensitivity, inadequate lung development during childhood or neonatal stage, genetic factors, and epigenetic mechanisms, among others [2,3]. The prevalence of COPD (adjusting for age, sex, ethnicity, education, pack-years smoked, body mass index, and altitude) was 11.9% in Mexico City and 19.4% in Montevideo [5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
