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. 2019 Jan 18;20(1):19.
doi: 10.1186/s12881-019-0751-9.

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

Iwona Gilowska  1 , Edyta Majorczyk  2 , Łukasz Kasper  3 , Katarzyna Bogacz  1 , Jan Szczegielniak  1 , Marta Kasper  4 , Jacek Kaczmarski  1 , Aleksandra Skomudek  1 , Marcin Czerwinski  1   5 , Krzysztof Sładek  3
Affiliations

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

Iwona Gilowska et al. BMC Med Genet. .

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; χ2 = 4.742, p = 0.02 for allele and 0.5% vs 3.9%, respectively; χ2 = 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%, χ2 = 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 < 0.0001), although independently of analyzed gene polymorphisms. Additionally, no correlation between parameters of lung function (FEV1% and FEV1/FVC) and protein level was found.

Conclusions: We found that -82G allele of SNP rs2276109 was associated with reduced risk of COPD, and COPD patients released more MMP-12 than healthy individuals, but independently on this SNP.

Keywords: COPD; ELISA; Genetics; Metalloproteinase 12; SNP.

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Conflict of interest statement

Ethics approval and consent to participate

The project was approved by the Ethics Committee of Opole Voivodship (No. 192/2012). Signed informed consent was obtained from all persons tested.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Alleles (a) and genotypes (b) distribution of − 82 A-to-G SNP of MMP-12 gene (rs2276109) in COPD patients and healthy control groups. Legend: COPD, patients with chronic obstructive pulmonary disease; CTR – controls; OR (95%CI) calculated for -82G allele in COPD patients-controls comparison was of 0.70 (0.51–0.95)
Fig. 2
Fig. 2
MMP-12 protein level in serum of COPD patients and healthy control groups. Legend: COPD, patients with chronic obstructive pulmonary disease; CTR – controls; data expressed as medians (25 and 75% percentiles)
Fig. 3
Fig. 3
MMP-12 gene polymorphism −82 A-to-G SNP impact on MMP-12 protein level in serum of COPD patients and healthy control groups (A, allele impact on MMP-12 protein level; B, genotype impact on MMP-12 protein level). Legend: COPD, patients with chronic obstructive pulmonary disease; CTR – controls; data expressed as medians (25 and 75% percentiles); no significant difference in mean MMP-12 protein levels between carriers with different − 82 A > G alleles/genotypes in one-way ANOVA test, Tuckey post-hoc test were not conducted
See this image and copyright information in PMC

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