Risk Effects of rs1799945 Polymorphism of the HFE Gene and Intergenic Interactions of GWAS-Significant Loci for Arterial Hypertension in the Caucasian Population of Central Russia

Abstract

The aim of this case-control replicative study was to investigate the link between GWAS-impact for arterial hypertension (AH) and/or blood pressure (BP) gene polymorphisms and AH risk in Russian subjects (Caucasian population of Central Russia). AH (n = 939) and control (n = 466) cohorts were examined for ten GWAS AH/BP risk loci. The genotypes/alleles of these SNP and their combinations (SNP-SNP interactions) were tested for their association with the AH development using a logistic regression statistical procedure. The genotype GG of the SNP rs1799945 (C/G) HFE was strongly linked with an increased AH risk (ORrecGG = 2.53; 95%CIrecGG1.03-6.23; ppermGG = 0.045). The seven SNPs such as rs1173771 (G/A) <i>AC026703.1</i>, rs1799945 (C/G) <i>HFE</i>, rs805303 (G/A) <i>BAG6</i>, rs932764 (A/G) <i>PLCE1</i>, rs4387287 (C/A) <i>OBFC1</i>, rs7302981 (G/A) <i>CERS5</i>, rs167479 (T/G) <i>RGL3</i>, out of ten regarded loci, were related with AH within eight SNP-SNP interaction models (<0.001 ≤ pperm-interaction ≤ 0.047). Three polymorphisms such as rs8068318 (T/C) <i>TBX2</i>, rs633185 (C/G) <i>ARHGAP42</i>, and rs2681472 (A/G) <i>ATP2B1</i> were not linked with AH. The pairwise rs805303 (G/A) <i>BAG6</i>-rs7302981 (G/A) <i>CERS5</i> combination was a priority in determining the susceptibility to AH (included in six out of eight SNP-SNP interaction models [75%] and described 0.82% AH entropy). AH-associated variants are conjecturally functional for 101 genes involved in processes related to the immune system (major histocompatibility complex protein, processing/presentation of antigens, immune system process regulation, etc.). In conclusion, the rs1799945 polymorphism of the <i>HFE</i> gene and intergenic interactions of <i>BAG6</i>, <i>CERS5</i>, <i>AC026703.1</i>, <i>HFE</i>, <i>PLCE1</i>, <i>OBFC1</i>, <i>RGL3</i> have been linked with AH risky in the Caucasian population of Central Russia.