Associations between Human Aldosterone Synthase (CYP11B2) and Angiotensin II type 1 Receptor (ATR1) Gene Polymorphisms with End Stage Renal Disease In hypertensive Egyptian Patients on Maintenance Hemodialysis

Abstract

Many people with an advanced form of kidney disease do not know they have weak or failing kidneys, but early detection and treatment can help prevent the progression of kidney disease to kidney failure. The resulting costs of treatment of ESRD are enormous. ESRD is a complex phenotype, which results from the presence of underlying kidney disease, and superimposing inherited and environmental factors. Among the predisposing genetic factors, renin-angiotensin-aldosterone system (RAAS) disruption is clearly involved in ESRD development. The aim of this study is to evaluate the association between CYP11B2 C-344T and ATR1 A1166C gene polymorphisms with increased risk for ESRD in hypertensive Egyptian patients on maintenance hemodialysis.This study included 70 ESRD patients on maintenance hemodialysis (32 males and 28 females, mean age 54.5± 9.5 years, recruited from El Doaah and El Rayan hospitals, Cairo, Egypt. 70 healthy individuals, of matching age and sex (30 males and 40 females, mean age 50.2 ± 13.1 years), were also included in the study. All subjects were genotyped for both CYP11B2 C-344T and ATR1 A1166C gene polymorphisms. Serum aldosterone was also measured for all subjects. Concerning the CYP11B2 gene, HD patients showed increased frequency of the TT genotype (68.57%) as compared to controls (only 12.85%), with no significant differences in T allele distribution between the 2 groups. In contrast, HD patients had low frequency of the CC genotype (5.71%) as compared to controls (32.85%), with a significant difference in C allele distribution between the HD patients (28.56%) and controls (70.7%). Comparing serum aldosterone levels in various CYP11B2 genotypes in HD patients revealed that patients with TT genotype had statistically higher aldosterone levels (121.583 ± 43.311) than those with the TC (72.055 ± 11.709) or CC genotype (68.75 ± 13.145). On the other hand, for AT1R A1166C genotype frequency, HD patients showed significantly (p˂0.05) higher frequency of CC genotype (70%) than controls (7.1%), with lower AA genotype frequency (5.71%) compared to controls (57%). Moreover, there was significant differences in A allele distribution between the HD patients (27.13%) and controls (64.25%).  The same was true for the C allele, with a frequency of (59.28%) in HD patients compared to a frequency of (39.25%) in controls. On the other hand, studying ATR1 A1166C gene polymorphisms revealed that patients with the CC genotype had significantly higher aldosterone levels (121.25 ± 43.006) than those with AA (87.6 ± 25.4) genotype.