Polymorphic locus rs1061624 of the ТNFR2 gene is associated with the development of arterial hypertension in males

Abstract

Aim To study the involvement of cytokine polymorphous loci in development of arterial hypertension (AH) in men from the Central Black Earth region of Russia.Materials and methods 821 men were evaluated, including 564 patients with AH and 257 individuals of the control group. Analysis of 8 cytokine mononucleotide polymorphisms (MNP) was performed using the real-time polymerase chain reaction with TagMan probes. Statistical analysis was performed with the STATISTICA (v.10.0) and PLINK (v.1.06) software. The regulatory potential of MNP was analyzed with the HaploReg (v.4.1) service (http://archive.broadinstitute.org).Results The rs1061624 ТNFR2 polymorphous locus was associated with development of AH in men in recessive (odd ratio (OR), 0.33; 95 % confidence interval (CI): 0.18–0.61, рperm=0.0004) and additive (OR, 0.50, 95 % CI: 0.34–0.74, рperm=0.0006) genetic models and exerted a protective effect in development of AH. The rs1061624 MNP of the ТNFR2 gene has a regulatory significance; it is located in the DNA sites hypersensitive to the action of DNAase 1 and in binding sites for transcriptional factors and histones that mark enhancers and promoters in different organs and tissues.Conclusion The rs1061624 ТNFR2 gene polymorphism is involved in the development of AH in men of the Central Black Earth region of Russia.

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

“…SNP HFE rs1799945 C > G has been correlated with medication agents acting on the renin-angiotensin system [80]. Importantly, Gill et al used a Mendelian randomization analysis of GWAS (48,972 European/Genetics of Iron Status Consortium) and PheWAS (424, 439 European/UK Biobank) summary data and founded a causal link between genetically determined levels of serum iron and a hazard of hypercholesterolemia and anemia [81]. The risk value of hypercholesterolemia for HTN (and in common for cardiovascular diseases) is well-known [6,82] and it is also revealed in the sample studied in this work.…”

“…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.)…”

Association Of Inflammation Gene Polymorphism With Increased Risk Of Metabolic Syndrome In Tatar Ethnic Group

“…The data about the association of the TNFRSF1B genes with MetS is absent. We found study reporting the association of TNFRSF1B with Crone disease, tuberculosis, arterial hypertension [43,44]. The association studies of TNFRSF1B were controversial.…”

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

“…The observed inconsistencies could stem from the differences in study designs (e.g., differences in the used covariates, sample sizes, gene–gene and gene-environment interactions, etc.). In addition, the differences in the results might be associated with ethnicity-specific pathogenetic features of the emergence and course of EH 32 – 37 or/and ethnicity-related differences in the genetic structure of the populations 38 , 39 .…”