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

Tatiana Ivanova; Maria Churnosova; Maria Abramova; Denis Plotnikov; Irina Ponomarenko; Evgeny Reshetnikov; Inna Aristova; Inna Sorokina; Mikhail Churnosov

doi:10.3390/ijms24097799

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

Int J Mol Sci. 2023 Apr 25;24(9):7799. doi: 10.3390/ijms24097799.

Authors

Tatiana Ivanova¹, Maria Churnosova¹, Maria Abramova¹, Denis Plotnikov², Irina Ponomarenko¹, Evgeny Reshetnikov¹, Inna Aristova¹, Inna Sorokina¹, Mikhail Churnosov¹

Affiliations

¹ Department of Medical Biological Disciplines, Belgorod State National Research University, 308015 Belgorod, Russia.
² Genetic Epidemiology Lab, Kazan State Medical University, 420012 Kazan, Russia.

Abstract

The aim of the study was directed at studying the sex-specific features of the correlation between genome-wide association studies (GWAS)-noticeable polymorphisms and hypertension (HTN). In two groups of European subjects of Russia (n = 1405 in total), such as men (n = 821 in total: n = 564 HTN, n = 257 control) and women (n = 584 in total: n = 375 HTN, n = 209 control), the distribution of ten specially selected polymorphisms (they have confirmed associations of GWAS level with blood pressure (BP) parameters and/or HTN in Europeans) has been considered. The list of studied loci was as follows: (PLCE1) rs932764 A > G, (AC026703.1) rs1173771 G > A, (CERS5) rs7302981 G > A, (HFE) rs1799945 C > G, (OBFC1) rs4387287 C > A, (BAG6) rs805303 G > A, (RGL3) rs167479 T > G, (ARHGAP42) rs633185 C > G, (TBX2) rs8068318 T > C, and (ATP2B1) rs2681472 A > G. The contribution of individual loci and their inter-locus interactions to the HTN susceptibility with bioinformatic interpretation of associative links was evaluated separately in men's and women's cohorts. The men-women differences in involvement in the disease of the BP/HTN-associated GWAS SNPs were detected. Among women, the HTN risk has been associated with HFE rs1799945 C > G (genotype GG was risky; OR_GG = 11.15 p_permGG = 0.014) and inter-locus interactions of all 10 examined SNPs as part of 26 intergenic interactions models. In men, the polymorphism BAG6 rs805303 G > A (genotype AA was protective; OR_AA = 0.30 p_permAA = 0.0008) and inter-SNPs interactions of eight loci in only seven models have been founded as HTN-correlated. HTN-linked loci and strongly linked SNPs were characterized by pronounced polyvector functionality in both men and women, but at the same time, signaling pathways of HTN-linked genes/SNPs in women and men were similar and were represented mainly by immune mechanisms. As a result, the present study has demonstrated a more pronounced contribution of BP/HTN-associated GWAS SNPs to the HTN susceptibility (due to weightier intergenic interactions) in European women than in men.

Keywords: GWAS; SNP; association; blood pressure; hypertension; sex.

MeSH terms

European People
Female
Genetic Predisposition to Disease
Genome-Wide Association Study*
Genotype
Humans
Hypertension* / genetics
Male
Molecular Chaperones / genetics
Plasma Membrane Calcium-Transporting ATPases / genetics
Polymorphism, Single Nucleotide

Substances

BAG6 protein, human
Molecular Chaperones
ATP2B1 protein, human
Plasma Membrane Calcium-Transporting ATPases

Grants and funding

This research received no external funding.