Polymorphisms of the matrix metalloproteinase genes are associated with essential hypertension in a Caucasian population of Central Russia

Abstract

AbstractThis study aimed to determine possible association of eight polymorphisms of sevenMMPgenes with essential hypertension (EH) in a Caucasian population of Central Russia. Eight SNPs of theMMP1,MMP2,MMP3,MMP7,MMP8,MMP9, andMMP12genes and their gene–gene (epistatic) interactions were analyzed for association with EH in a cohort of 939 patients and 466 controls using logistic regression and assuming additive, recessive, and dominant genetic models. The functional significance of the polymorphisms associated with EH and 114 variants linked to them (r2 ≥ 0.8) was analyzed in silico. Allele G of rs11568818MMP7was associated with EH according to all three genetic models (OR = 0.58–0.70, pperm = 0.01–0.03). The above eight SNPs were associated with the disorder within 12 most significant epistatic models (OR = 1.49–1.93, pperm < 0.02). Loci rs1320632MMP8and rs11568818MMP7contributed to the largest number of the models (12 and 10, respectively). The EH-associated loci and 114 SNPs linked to them had non-synonymous, regulatory, and eQTL significance for 15 genes, which contributed to the pathways related to metalloendopeptidase activity, collagen degradation, and extracellular matrix disassembly. In summary, eight studied SNPs ofMMPsgenes were associated with EH in the Caucasian population of Central Russia.