Polymorphisms of the matrix metalloproteinase 9 gene are associated with duodenal ulcer in a Caucasian population of Central Russia

Objectives: The aim of this study was to analyze functionally significant polymorphisms of matrix metalloproteinases genes (MMP-1, -2, -3, -8, -9) for their association with duodenal ulcer (DU) in the Caucasian population from Central Russia. Methods: The study sample included 364 DU patients (208 had H. pylori and 156 were uninfected) and 347 controls (H. pylori-negative). Ten polymorphisms of the MMP-1, -2, -3, -8, -9 genes were examined for association with DU by the logistic regression analysis (used the three main genetic models). The polymorphisms of the MMP-9 gene associated with DU and 59 proxy variants (r2 > 0.80) were studied in silico for their functionality. Results: Allele G of rs17576 and haplotype GG [rs17576-rs3787268] of the MMP-9 gene may increase risk for DU (adjOR = 1.46-2.09, pperm < 0.006 and adjOR = 1.60, pperm = 0.016 respectively). Five SNPs of the MMP-9 gene may increase risk for H. pylori-positive DU: alleles T of rs3918242 (adjOR = 1.95, pperm = 0.007), G of rs17576 (adjOR = 1.68-2.81, pperm < 0.002), and A of rs17577 (adjOR = 1.96, pperm = 0.008), haplotypes GG [rs17576-rs3787268] (adjOR = 1.95, pperm = 0.006) and GGC [rs17576-rs3787268-rs2250889] (adjOR = 1.96, pperm = 0.006). These loci and 59 proxy SNPs may have functionally significant epigenetic effects, amino acid replacements in the MMP9, and correlate with the expression and alternative splicing of 17 and 6 genes respectively. Conclusions: Polymorphisms rs17576 and rs3787268 of the MMP-9 were associated with DU and five MMP-9 gene SNPs were associated with H. pylori-related DU in Caucasians of Central Russia. (c) 2022 The Authors. Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).