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

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.

The “Slow Horse Racing Effect” on Lung Function in Adult Life in Chronic Obstructive Pulmonary Disease Associated to Biomass Exposure

“…This information is particularly relevant in the Mexican cohort of women whose average height is 148 cm, which is notably lower than smokers (men and women) studied by Burrows. In this sense, studies performed in women exposed to biomass showed that genetic susceptibility (57)(58)(59)(60) together with the socioeconomic context may influence growth and decrease lung function, as previously demonstrated by some reports (61)(62)(63).…”

<p>Heterozygous Genotype rs17580 AT (PiS) in <em>SERPINA1</em> is Associated with COPD Secondary to Biomass-Burning and Tobacco Smoking: A Case–Control and Populational Study</p>

“…33 In the present study, we observe that the minor allele (T) of rs17580 (PiS) is associated with COPD in both comparisons, tobacco smoking, and exposure to biomass-burning smoke. This polymorphism was reported by our workgroup associated with lower values in lung function among smokers, 27 but not with the genetic susceptibility to the disease, probably due to small sample size; current analysis in addition to twocomparisons with two different risk exposure factors includes a better case-control ratio, almost 1:3 in each comparison. These results lead us to the question about the frequency of risk alleles among Mexican people, in which ancestral contribution has been marked by an admixture between Caucasian and indigenous (Amerindian) populations.…”

“…In the current study, we have assessed the genetic susceptibility associated with PiS and PiZ variants evaluated by molecular techniques that let us know the state of genotypes for each protein variant. Previously, among smokers, we found the rs17580 AT genotype associated with a decreased FEV 1 /FVC ratio compared to subjects with the homozygous AA genotype, 27 and recently, two SNPs (rs709932 and rs1303) in the SERPINA1 gene too, forming a haplotype shaped by both common alleles (CT haplotype) associated with reduced risk for COPD. 28 However, investigations have focused on the PiS and PiZ variants; individuals SS, SZ, and ZZ express serum concentrations of 85%, 25%, and 15% of the protein, respectively, compared to the normal levels (MM phenotype).…”

DNA Methylation: A Potential Biomarker of Chronic Obstructive Pulmonary Disease

“…Hypomethylation of SERPINA1 and fucosyltransferase-7 ( FUT7 ) genes was found to be closely related to COPD and pulmonary dysfunction. Recently, the haplotypes of two major alleles of SERPINA1 were found to be related to reduced risk of COPD ( Ponce-Gallegos et al, 2019 ). SERPINA1 gene encodes a sialic acid protein called α-1 antitrypsin (AAT), whose main function is to protect the lower respiratory tract from degradation by neutrophil elastase ( Salahuddin, 2010 ).…”