基质金属蛋白酶 9 基因的功能性显著多态性与俄罗斯中部白种人幽门螺杆菌阳性胃溃疡的关联。
Association of the functionally significant polymorphisms of the MMP9 gene with H. pylori-positive gastric ulcer in the Caucasian population of Central Russia.
机构信息
Department of Life Sciences, College of Science and General Studies, Alfaisal University, Riyadh, Saudi Arabia.
Department of Medical Biological Disciplines, Belgorod State University, Belgorod, Russia.
出版信息
PLoS One. 2021 Sep 7;16(9):e0257060. doi: 10.1371/journal.pone.0257060. eCollection 2021.
BACKGROUND AND PURPOSE
The study analyzed the association of functionally significant polymorphisms of matrix metalloproteinases (MMPs) genes with the development of gastric ulcer (GU) in Caucasians from Central Russia.
METHODS
The 781 participants, including 434 patients with GU (196 Helicobacter pylori (H. pylori)-positive and 238 H. pylori-negative) and 347 controls (all H. pylori-negative) were recruited for the study. Ten SNPs of the MMP1 (rs1799750), MMP2 (rs243865), MMP3 (rs679620), MMP8 (rs1940475), and MMP9 (rs3918242, rs3918249, rs3787268, rs17576, rs17577, and rs2250889) genes were considered for association with GU using multiple logistic regression. The SNPs associated with GU and loci linked (r2≥0.8) to them were analyzed in silico for their functional assignments.
RESULTS
The SNPs of the MMP9 gene were associated with H. pylori-positive GU: alleles C of rs3918249 (OR = 2.02, pperm = 0.008) and A of rs3787268 (OR = 1.60-1.82, pperm ≤ 0.016), and eight haplotypes of all studied MMP9 gene SNPs (OR = 1.85-2.04, pperm ≤ 0.016) increased risk for H. pylori-positive GU. None of the analyzed SNPs was independently associated with GU and H. pylori-negative GU. Two haplotypes of the MMP9 gene (contributed by rs3918242, rs3918249, rs17576, and rs3787268) increased risk for GU (OR = 1.62-1.65, pperm ≤ 0.006). Six loci of the MMP9 gene, which are associated with H. pylori-positive GU, and 65 SNPs linked to them manifest significant epigenetic effects, have pronounced eQTL (17 genes) and sQTL (6 genes) values.
CONCLUSION
SNPs of the MMP9 were associated with H. pylori-positive GU but not with H. pylori-negative GU in Caucasians of Central Russia.
背景与目的
本研究分析了基质金属蛋白酶（MMPs）基因功能显著多态性与白种人（俄罗斯中部）发生胃溃疡（GU）的相关性。
方法
本研究纳入了 781 名参与者，包括 434 名 GU 患者（196 名 H. pylori 阳性，238 名 H. pylori 阴性）和 347 名对照者（均为 H. pylori 阴性）。我们对 MMP1（rs1799750）、MMP2（rs243865）、MMP3（rs679620）、MMP8（rs1940475）和 MMP9（rs3918242、rs3918249、rs3787268、rs17576、rs17577 和 rs2250889）10 个基因的 SNP 与 GU 进行了关联分析，采用多元逻辑回归进行分析。将与 GU 相关且与它们连锁（r2≥0.8）的 SNP 进行了在体分析，以确定其功能。
结果
MMP9 基因的 SNP 与 H. pylori 阳性 GU 相关：rs3918249 的 C 等位基因（OR=2.02，pperm=0.008）和 rs3787268 的 A 等位基因（OR=1.60-1.82，pperm≤0.016），以及所有研究 MMP9 基因 SNP 的 8 个单倍型（OR=1.85-2.04，pperm≤0.016）增加了 H. pylori 阳性 GU 的风险。分析的 SNP 均与 GU 和 H. pylori 阴性 GU 无关。MMP9 基因的两个单倍型（由 rs3918242、rs3918249、rs17576 和 rs3787268 贡献）增加了 GU 的风险（OR=1.62-1.65，pperm≤0.006）。与 H. pylori 阳性 GU 相关的 MMP9 基因的 6 个位点，以及与其连锁的 65 个 SNP，均表现出显著的表观遗传效应，有明显的 eQTL（17 个基因）和 sQTL（6 个基因）值。
结论
MMP9 的 SNP 与俄罗斯中部白种人 H. pylori 阳性 GU 相关，但与 H. pylori 阴性 GU 无关。
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