The role of obesity in the implementation of genetic predisposition to the development of essential hypertension in men

Abstract

BACKGROUND: Obesity is considered a non-infectious pandemic, and the increase in its spread is a serious medical and social problem. High values of body mass index closely correlate with arterial hypertension and its complications, but the effect of obesity on the realization of hereditary susceptibility to essential hypertension (EH) remains poorly understood.
 AIMS: To study the associations of polymorphic loci of MMPs with the development of EH in men depending on the presence of obesity.
 MATERIALS AND METHODS: The study was conducted in a case-control design. Surveyed 821 men 564 patients with hypertension and 257 patients of the control group. Groups of patients and controls were divided into subgroups depending on the presence of obesity. All men were genotyped for eight polymorphic loci of MMPs. Nonsynonymous SNPs were detected using the software SIFT (https://sift.bii.a-star.edu.sg/). The regulatory potential was studied using the HaploReg service (https://pubs.broadinstitute.org/mammals/haploreg/haploreg.php). The association of SNPs with the expression level was detected using GTEx-portal (http://www.gtexportal.org).
 RESULTS: It was found that in obese men allele A (OR=2.01; p=0.01) and genotype GG (OR=0.42, p=0.01) of rs11568818 MMP7 are associated with the essential hypertension. In men without obesity allele 6A (OR=1.32; p=0.04) of rs3025058 MMР3 and genotypes GG (OR=1.52; p=0.04) and GA (OR=0.63; p=0.03)) of rs17577 MMP9 are associated with the development of the disease. These SNPs located in region of promoter and enhancer histone marks, in the region of hypersensitivity to DNAse-1, in binding sites of regulatory proteins and transcription factors. These SNPs associated with the level of gene expression.
 CONCLUSIONS: In this study we established associations with the development of EH of SNP rs11568818 MMP7 in obese men and of SNPs rs3025058 MMР3 and rs17577 MMP9 in non-obese men.

Sex-Specific Features of the Correlation between GWAS-Noticeable Polymorphisms and Hypertension in Europeans of Russia

“…The influence of hereditary factors on the HTN occurrence has been studied for a long time and, at present, the genetic contribution to the disease formation has been confirmed in numerous works performed on the basis of twin/family [11][12][13][14][15][16][17], GWAS ([9,10,18-34], etc.) and other associative (based on the candidate genes' analysis) ( [35][36][37][38][39][40][41][42][43][44][45][46][47][48], etc.) studies.…”

“…are shown, including the taking into account of the action of sex-specific risk factors of the disease such as obesity, smoking, etc. [40,[45][46][47][48] (etc.). In addition, significant men-women differences in sex hormone genetic traits [52][53][54], BMI genetic traits (obesity, waist/hip circumference, etc.)…”