PP.28.14

Abstract

Objective: To investigate for the first time in the South-Eastern population the possible association of seven polymorphic variants from genome-wide association studies (GWASs) with essential hypertension (EH): rs890283, rs2229238, rs1173771, rs9349379, rs3918226, rs2681472, rs579459, in or near the genes CYP2J2, IL6R, NPR3 - C5orf23, PHACTR1, eNOS, ATP2B1, ABO, respectively, and to further explore the epistasis interactions that are involved in the pathophysiology of high blood pressure. Design and method: 794 Bulgarian subjects were included: 496 normotensive (population controls) and 298 hypertensive. Genomic DNA was extracted from venous blood samples. Chemagic Magnetic Separation Module I was used to prepare the isolation step. All variants were genotyped with TaqMan Allelic Discrimination Assays and the epistasis interaction was analyzed. We used χ2 test and generalized multifactor dimensionality reduction (GMDR) analysis to identify the models of genotype interaction. Data were analyzed with PLINK v1.07. Results: Genotype frequencies for all polymorphisms in controls and in patients with EH were in Hardy-Weinberg equilibrium (p > 0.05). In single-locus analysis, the rs9349379 in PHACTR1 gene demonstrated significant association in recessive model with susceptibility to EH in the female subgroup (OR 1.68, 95%CI 1.15–2.46; p = 0.009), whereas rs11646213 in CDH13 gene was more common in female controls than in female hypertensive patients in the same model (OR 0.36, 95%CI 0.14–0.95; p = 0.035). Generalized multifactor dimensionality reduction analysis demonstrated that there exist significant interactions between the studied polymorphisms (Table).Conclusions: The results of this epistasis study indicates a significant association between the studied polymorphic variants and essential hypertension in the Bulgarian population.