Abstract
Published data on the association between MMP-9 polymorphisms (−1562 C > T, rs3918242; Gln279Arg, rs17576 Arg668Gln, rs17577) and asthma susceptibility are inconclusive. To derive a more precise estimation of this association, a meta-analysis was performed. A literature search was conducted in PubMed, Web of Science, EMBASE, Wanfang, and China National Knowledge Infrastructure (CNKI) databases to identify eligible studies. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to calculate the strength of association. Sensitivity analysis was performed to evaluate the influence of individual studies on the overall effect estimates, and funnel plots and Egger's test were inspected for indication of publication bias. Seven studies with 1592 asthma patients and 1987 controls were finally identified. Overall, we found no significant association between −1562 C > T, rs3918242 polymorphism, and asthma susceptibility in any of the genetic model comparisons. After categorizing studies into different subgroups on the basis of ethnicity and age, there is still no significant association. For the Gln279Arg, rs17576 polymorphism, there seems to be a significant association in the allelic genetic model in regard to the P value (OR = 1.11, 95% CI = 1.00–1.22, I 2 = 0%, P (Z)=0.044); however, the value of lower 95% CI is 1.0. For the Arg668Gln, rs17577 polymorphism, a high significant association was observed in the dominant model comparison (OR = 1.65, 95% CI = 1.28–2.11, I 2 = 22.50%, P (Z)=0), recessive model comparison (OR = 2.40, 95% CI = 1.23–4.72, I 2 = 0%, P (Z)=0.011), homozygote genotype comparison (OR = 2.69, 95% CI = 1.36–5.33, I 2 = 0%, P (Z)=0.004), and allelic genetic model (OR = 1.59, 95% CI = 1.29–1.97, I 2 = 36.9%, P (Z)=0). Sensitivity analysis demonstrated the stability of our results, and publication bias was not evident. The present meta-analysis suggests that MMP-9 Arg668Gln, rs17577 polymorphism may be the risk factor for asthma susceptibility.
Highlights
Asthma is a chronic respiratory inflammation disease characterized by airway hyperresponsiveness, reversible airway obstruction, and airway wall remodelling, which is associated with significant thickening of the reticular basement membrane and deposition of the extracellular matrix components [1,2,3]
At least twelve potential clinically relevant SNPs were found in the promoter and coding region, which are important for the matrix metalloproteinases (MMP)-9 expression and function [16,17,18]. erefore, a lot of genetic epidemiology studies have assessed the association of MMP-9 gene polymorphisms and susceptibility of asthma in different populations [19,20,21,22,23,24,25,26]
Publications were searched using the Pubmed, EMBASE, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases. e search strategy utilized in our study was as follows: asthma or asthmatic and matrix metalloproteinase 9 or MMP-9 or Gelatinase B in combination with polymorphism or mutation or variant
Summary
Asthma is a chronic respiratory inflammation disease characterized by airway hyperresponsiveness, reversible airway obstruction, and airway wall remodelling, which is associated with significant thickening of the reticular basement membrane and deposition of the extracellular matrix components [1,2,3]. In this regard, matrix metalloproteinases (MMP) family, which is a Zn2+- and Ca2+-dependent endopeptidases, plays a vital role in degradation of extracellular matrix components [4]. These results were inconclusive and inconsistent. erefore, we performed a meta-analysis of all eligible studies to obtain more precise estimation of the association of MMP-9 gene polymorphisms including three SNPs (−1562 C > T, rs3918242; Gln279Arg, rs17576, and Arg668Gln, rs17577) with asthma susceptibility
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