Sex-specific features of interlocus interactions determining susceptibility to hypertension

Abstract

Background: Hypertension (HT) belongs to a group of widespread diseases in both men and women, but at the same time the disease is more often registered (≈20%) in men than in women. Genetic factors determining the sex characteristics of the prevalence of HT are largely unknown. The aim of the study: To establish sex-specific features of intergenic interactions of GWAS-significant loci determining susceptibility to HT. Materials and methods: The sample of men included 564 patients with HT and 257 controls (total sample size n=821), women – 375 patients with HT and 209 controls (total sample size n=584). Genotyping of 10 polymorphisms that showed associations with HT (blood pressure (BP)) in previously conducted genome-wide studies (GWAS) was performed. The intergenic interactions determining the susceptibility to HT in men and women were evaluated by the MB-MDR method. Results: In men, susceptibility to HT is determined by the interlocus interaction rs932764- PLCE1 × rs7302981-CERS5 × rs1799945-HFE × rs8068318-TBX2 (Wald St. = 32.12 pperm =0.001) with the most pronounced effect of two-locus interaction rs1799945-HFE × rs8068318-TBX2 (determines 0.76% of entropy). Among women, the most significant in relation to HT is the four-locus model, which includes polymorphic loci rs932764-PLCE1 × rs8068318-TBX2 × rs1173771- AC026703.1 × rs167479-RGL3 (Wald St. = 33.53 pperm <0.001) with the maximum contribution to the entropy of the disease (2.26%) of the pair interaction rs8068318-TBX2 × rs167479-RGL3. Polymorphisms rs932764-PLCE1 and rs8068318-TBX2 are very significant in both men and women. Conclusion: The intergenic interactions of HT-significant GWAS loci are sex-specific.