Dataset Information

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.

SUBMITTER: Ponce-Gallegos MA

PROVIDER: S-EPMC6982076 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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

Ponce-Gallegos Marco Antonio MA Pérez-Rubio Gloria G García-Carmona Adriana A García-Gómez Jesús J Hernández-Zenteno Rafael R Ramírez-Venegas Alejandra A Falfán-Valencia Ramcés R

International journal of molecular sciences 20191227 1

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 we ...[more]

PMID: 31892136

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Project description:Type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic pathologies in the world. In developing countries, such as Mexico, its prevalence represents an important public health and research issue. Determining factors triggering T2DM are environmental and genetic. While diet, exercise and proper weight control are the first measures recommended to improve the quality of life and life expectancy of patients, pharmacological treatment is usually the next step. Within every population there are variations in interindividual drug response, which may be due to genetic background. Some of the most frequent first line T2DM treatments in developing countries are sulfonylureas (SU), whose targets are ATP-sensitive potassium channels (KATP). Single nucleotide polymorphisms (SNPs) of the KATP coding genes, potassium voltage-gated channel subfamily J member 11 (KCNJ11) and ATP binding cassette subfamily C member 8 (ABCC8) have been associated with SU response variability. To date, there is little information regarding the mechanism by which these SNPs work within Mexican populations. The present study describes the distribution of three SNPs [KCNJ11 rs5219 (E23K), ABCC8 rs757110 (S1369A) and rs1799854 (-3C/T)] among Mestizo Mexican (MM) T2DM patients, and compares it with published data on various healthy subjects and T2DM populations. Through this comparison, no difference in the KCNJ11 rs5219 and ABCC8 rs757110 allelic and genotypic frequencies in MM were observed compared with the majority of the reported populations of healthy and diabetic individuals among other ethnic groups; except for African and Colombian individuals. By contrast, ABCC8 rs1799854 genomic and allelic frequencies among MM were observed to be significantly different from those reported by the 1000 Genomes Project, and from diabetic patients within other populations reported in the literature, such as the European, Asian and Latin-American individuals [T=0.704, G=0.296; CC=0.506, CT=0.397, TT=0.097; 95% confidence interval (CI); P?0.05]; except for South Asian and Iberian populations, which may reflect the admixture origins of the present Mexican population. This genetic similarity has not been observed in the other Latin-American groups. To the best of our knowledge, this is the first study of ABCC8 rs757110 and rs1799854 SNP frequencies in any Mexican population and, specifically with diabetic Mexicans. Knowledge of the genetic structure of different populations is key to understanding the interindividual responses to drugs, such as SU and whether genotypic differences affect clinical outcome.

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Dataset Information

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

Publications

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

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