AGT, ACE, AGTR1, UMOD AND ADIPOQ GENES POLYMORPHISMS INTERACTIONS IN PREHYPERTENSION

Abstract

Abstract Objective: Prehypertension (PHT) is recognized as a cardio-renal risk factor, and associated with progression to hypertension (HT). Studies of the genetic background of PHT have not been fully elucidated and the results suggested a possible role of genes involved in the etiopathogenesis of HT. The lack of data has prompted this study to hypothesize that hypertension and metabolic syndrome-related AGT rs2004776, ACE rs1799752, AGTR1 rs5186, UMOD rs13333226, ADIPOQ rs266729 and rs17300539 gene polymorphisms are more commonly found in subjects with PHT, than in subjects with optimal and normal blood pressure (BP). Design and method: A total of 601 subjects were included in this cross-sectional, observational study; 319 with high normal BP (PHT, 120–139/80–89 mmHg), ages 20–45, and 282 individuals with normal and optimal BP as a control group (NT). Results: The results indicated that the AGT, ACE, AGTR1, UMOD, and ADIPOQ gene polymorphisms were not found more frequently in PHT subjects than in NT. A significant difference was found in the number of rs266729 ADIPOQ heterozygous carriers; there were less carriers in the PHT group (35.1%) than in the NT group (44.7%), P < 0.03. The significance of the heterozygous model (CG vs GG/CC) of rs266729 ADIPOQ polymorphism in PHT in terms of reduced risk was observed (OR 0.66; 95% CI 0.47–0.92; P = 0.01). PHT was significantly associated with following haplotypes: hIAGCA ACE:UMOD:ADIPOQ_rs17300539:ADIPOQ_rs266729:AGTR1 (OR 1.56; 95%CI 1.08–2.24; P = 0.02), hIAGC ACE:UMOD:ADIPOQ_rs17300539:ADIPOQ_rs266729 (OR 1.45; 95%CI 1.07–1.96; P = 0.02), hIAG ACE:UMOD:ADIPOQ_rs17300539 (OR 1.30; 95%CI 1.00–1.68; P = 0.05), hAGC UMOD:ADIPOQ_rs17300539:ADIPOQ_rs266729 (OR 1.37; 95%CI 1.07–1.77; P = 0.01) and hAG UMOD:ADIPOQ_rs17300539 (OR 1.42; 95%CI 1.07–1.90; P = 0.02). Results emphasized two significant models of gene-gene-other determinants interactions with PHT, one model included creatinine, total cholesterol, alpha-1-microglobulin, ADIPOQ rs17300539 and UMOD rs13333228; and the second model includes ADIPOQ rs17300539, AGT rs2004776, cardiovascular risk, sex, BMI, and the gene-gene interaction AGTR1:ADIPOQ_rs266729:UMOD:ACE. Conclusions: The finding of five significantly related gene-gene interactions, as well as the discovery of their haplotypes that increase the PHT risk, and the finding of two gene-gene-other determinants interactions models, confirmed the good selection of genes, particularly UMOD and ADIPOQ, involved in various biological pathways responsible for controlling BP.