The study of the associations of polymorphism of matrix metalloproteinases with multifactorial human diseases and in silico assessment of their functional effects

Abstract

The objective of this study is to identify the associations of polymorphism of matrix metalloproteinase genes with multifactorial diseases and evaluate in silico their functional effects. The material for the study was genomic DNA isolated from venous blood samples by the standard phenol-chloroform extraction method. The rs2250889 MMP9, rs11568818 MMP7 and rs17576 MMP9 polymorphic loci were studied using the polymerase chain reaction on a CFX-96 Real-Time System thermal cycler (Bio-Rad Laboratories, Inc., US) using oligonucleotide primers and probes synthesized by Syntol LLC, Russia). It was established that the rs2250889 MMP9 polymorphic locus is associated with the development of primary open-angle glaucoma (OR=0.67-1.44, p=0.02-0.04), the rs11568818 MMP7 locus - with arterial hypertension (OR=0.69-0.84, p=0.03), the rs17576 MMP9 locus - with peptic ulcer (OR=1.24, p=0.04). With the help of HaploReg (v4.1), it was shown that all three SNPs have a pronounced regulatory potential - they are located in DNA regions associated with histones marking enhancers and promoters in the binding sites of regulatory proteins - TBP, c-FOS, c-Jun and CTCF, in regions of regulatory DNA motifs, where binding to transcription factors occurs.

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