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The role of MMP-12 gene polymorphism?-?82 A-to-G (rs2276109) in immunopathology of COPD in polish patients: a case control study.

ABSTRACT: BACKGROUND:Major symptoms of chronic obstructive pulmonary disease (COPD) are chronic bronchitis and emphysema leading from lung tissue destruction, that is an effect of an imbalance between metalloproteinases (MMPs) and their tissue inhibitors activity. As potential factor involved in this COPD pathogenesis, MMP-12 is considered. We investigated the role of genetic polymorphism and protein level of MMP-12 in the COPD development among Poles. METHODS:We analyzed -?82 A?>?G SNP in the promoter region of MMP-12 gene (rs2276109) among 335 smoked COPD patients and 309 healthy individuals, including 110 smokers. Additionally, 60 COPD patients and 61 controls (23 smokers) were tested for serum levels of MMP-12 using ELISA. All subjects were analyzed for lung function using spirometry (FEV1% and FEV1/FVC parameters). RESULTS:We observed that -82G allele and -82GG homozygous genotype frequencies of the SNP rs2276109 were significantly lower in COPD patients than in controls (12.5% vs 16.9%, respectively; ?2?=?4.742, p?=?0.02 for allele and 0.5% vs 3.9%, respectively; ?2?=?9.0331, p?=?0.01 for genotype). Moreover, -82G allele was more frequent in controls smokers than in non-smokers (22.3% vs 14.1%, ?2?=?6.7588, p?=?0.01). Serum level of MMP-12 was significantly higher in COPD patients than in controls groups (6.8?ng/ml vs 3.3?ng/ml, respectively; F?=?7.433, p?

SUBMITTER: Gilowska I

PROVIDER: S-EPMC6339316 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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The role of MMP-12 gene polymorphism - 82 A-to-G (rs2276109) in immunopathology of COPD in polish patients: a case control study.

Gilowska Iwona I Majorczyk Edyta E Kasper Łukasz Ł Bogacz Katarzyna K Szczegielniak Jan J Kasper Marta M Kaczmarski Jacek J Skomudek Aleksandra A Czerwinski Marcin M Sładek Krzysztof K

BMC medical genetics 20190118 1

<h4>Background</h4>Major symptoms of chronic obstructive pulmonary disease (COPD) are chronic bronchitis and emphysema leading from lung tissue destruction, that is an effect of an imbalance between metalloproteinases (MMPs) and their tissue inhibitors activity. As potential factor involved in this COPD pathogenesis, MMP-12 is considered. We investigated the role of genetic polymorphism and protein level of MMP-12 in the COPD development among Poles.<h4>Methods</h4>We analyzed - 82 A > G SNP in ...[more]

PMID: 30658596

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Project description:Background Genetic variants influencing lung function or immune system may be involved in the development of asthma and/or its symptoms. Matrix metalloproteinases (MMPs) contribute to both normal and pathological tissue remodeling and also act as regulatory molecules by processing cytokines or adhesion molecules. In animal models, growing evidences suggest that MMPs play important roles in asthma phenotypes. Some MMP genes (e.g. MMP-9 and MMP-12) have recently been shown to be associated with asthma in Caucasian populations. We investigated whether single nucleotide polymorphisms (SNPs) in MMP-7 and MMP-12 could affect the susceptibility to and clinical phenotypes of asthma in the Japanese population. Methods We conducted a case-control study between SNPs in MMP-7 and MMP-12 genes and asthma-related phenotypes using childhood and adult Japanese populations (653 childhood asthma patients and 423 controls, and 428 adult asthma patients and 646 controls, respectively). To investigate the effects of amino acid substitutions by SNPs on MMPs' enzymatic activity, MMP activity assays were performed using commercially available kits based on fluorescence resonance energy transfer (FRET) peptide. We also evaluated the effect of 3’UTR SNP in MMP-7 on its mRNA stability and the effect of SNP in MMP-12 on its antimicrobial activity. Results We found that, in the Japanese population, SNPs of MMP-7 (rs10502001, G/A, Arg77His; rs14983, C/T, 3’UTR) (P = 0.006; odds ratio (OR), 1.46; 95% confidential interval (CI), 1.126-1.903) and MMP-12 (rs652438, A/G, Asn357Ser) (P = 0.015; OR, 1.60; 95% CI, 1.002-2.556) showed significant association with adult and childhood asthma, respectively. We also found that the SNP (rs652438) in MMP-12 was associated with severity in adult asthma (P = 0.010). Using supernatant from cultured HEK293 cells stably transfected with the pcDNA3.1(+)-MMP-7 or MMP-12 as MMP proteins, we evaluated activation kinetics, rate of proteolytic cleavage of FRET peptide, Michaelis constant, and substrate specificity of the enzyme. In this system, we couldn't detect the functional effects of amino acid substitutions by SNPs on the enzymatic activity. Conclusions Our association study suggested that genetic variants of MMP7 and MMP12 conferred risk for development of asthma in the Japanese population.

Dataset Information

The role of MMP-12 gene polymorphism?-?82 A-to-G (rs2276109) in immunopathology of COPD in polish patients: a case control study.

Publications

The role of MMP-12 gene polymorphism - 82 A-to-G (rs2276109) in immunopathology of COPD in polish patients: a case control study.

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