Haplotype in SERPINA1 (AAT) Is Associated with Reduced Risk for COPD in a Mexican Mestizo Population.

Marco Antonio Ponce-Gallegos,Rafael Hernández-Zenteno,Adriana García-Carmona,Jesús García-Gómez,Ramcés Falfán-Valencia,Alejandra Ramírez-Venegas,Gloria Pérez-Rubio

doi:10.3390/ijms21010195

Abstract

Protease inhibitor S (PiS) and protease inhibitor Z (PiZ) variants in the SERPINA1 gene are the main genetics factors associated with COPD; however, investigations about other polymorphisms are scanty. The aim of this study was to evaluate two missense single nucleotide polymorphisms (SNPs) (rs709932 and rs1303) in the SERPINA1 gene in Mexican mestizo patients with chronic obstructive pulmonary disease (COPD) related to tobacco smoking and biomass-burning exposure. 1700 subjects were genotyped and divided into four groups: COPD related to tobacco smoking (COPD-S, n = 297), COPD related to biomass-burning exposure (COPD-BB, n = 178), smokers without COPD (SWOC, n = 674), and biomass-burning exposed subjects (BBES, n = 551) by real-time PCR. Moreover, the patients’ groups were divided according to their exacerbations’ frequency. We carried out a haplotype analysis. We did not find differences in allele and genotype frequencies between groups in unadjusted and adjusted analyses, neither with these SNPs and lung function decline. Exacerbations’ frequency is not associated with these SNPs. However, we found a haplotype with major alleles (CT) associated with reduced risk for COPD (p < 0.05). Our analysis reveals that SNPs different from PiS and PiZ (rs709932 and rs1303) in the SERPINA1 gene are not associated with COPD and lung function decline in a Mexican mestizo population. However, a haplotype shaped by both major alleles (CT haplotype) is associated with reduced risk for COPD.

Highlights

In accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD), Chronic Obstructive Pulmonary Disease (COPD) is a common, preventable, and treatable disease characterized by persistent respiratory symptoms and airflow limitation
Our aim was to study two single nucleotide polymorphisms (SNPs) in SERPINA1 different from Protease inhibitor S (PiS) and protease inhibitor Z (PiZ) in a Mexican mestizo population with COPD related to tobacco smoking and biomass-burning exposure
One thousand and seven hundred subjects were included in two cases groups and two control groups; 297 patients with COPD related to tobacco smoking (COPD-S), 178 patients with COPD related to biomass burning smoke exposure (COPD-BB), 674 smokers without COPD (SWOC), and 551 biomass-burning exposed subjects without COPD (BBES)

Summary

Introduction

In accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD), Chronic Obstructive Pulmonary Disease (COPD) is a common, preventable, and treatable disease characterized by persistent respiratory symptoms and airflow limitation. These conditions are mainly caused by significant exposure to noxious particles or gases, being the most important tobacco smoking and biomass-burning exposure [1]. Alpha-1 antitrypsin deficiency (AATd) is the most important genetic risk factor associated with COPD [4]. The common genotype for SERPINA1 (AAT) is described as PiMM and by protein serum levels between 150 and 350 mg/100 mL. It has been previously described that individuals carrying on SS, SZ, and ZZ genotypes express serum protein concentrations of 85%, 25%, and 15%, respectively [6]

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Results