Angiotensinogen Gene Missense Polymorphisms (rs699 and rs4762): The Association of End-Stage Renal Failure Risk with Type 2 Diabetes and Hypertension in Egyptians
Open Access
- 25 February 2021
- Vol. 12 (3), 339
- https://doi.org/10.3390/genes12030339
Abstract
Type 2 diabetes mellitus (T2DM) and hypertension are common chronic diseases mainly associated with the development and progression of end-stage renal disease (ESRD) leading to morbidity and mortality. Gene polymorphisms linked to the renin–angiotensin (AGT)–aldosterone system (RAAS) were broadly inspected in patients with diabetic nephropathy (DN) and hypertension. This study aimed to investigate the association of AGT gene polymorphisms (rs699 and rs4762) with ESRD in T2DM hypertensive Egyptian patients. Genotyping of rs699 and rs4762 was conducted using the tetra-primers amplification refractory mutation system (ARMS-PCR). The allelic distribution analysis was performed on 103 healthy control subjects, 97 non-ESRD patients, and 104 patients with ESRD. The allelic frequencies of AGT gene polymorphisms (rs4762 and rs699) in all study participants were assessed. For the non-ESRD group, the frequencies of the alleles of AGT-rs4762 (χ2 = 31.88, p < 0.001, OR = 5.17, CI 95%: 2.81–9.51) and AGT-rs699 (χ2 = 4.85, p = 0.027, OR = 1.56, CI 95%: 1.05–2.33) were significantly associated with the non-ESRD group. However, for the ESRD group, the T allele was significantly higher than that in the controls (χ2 = 24.97, p < 0.001, odds ratio (OR) = 4.35, CI 95%: 2.36–8.02). Moreover, AGT (rs699) genotypes showed no significant difference between the ESRD group and controls. In conclusion, AGT gene polymorphisms rs699 and rs4762 were associated with non-ESRD versus controls, without any significant risk observed in all patient groups. However, the AGT (rs4762) variant showed a significant risk in the ESRD group in comparison to controls in Egyptians.This publication has 48 references indexed in Scilit:
- The association of the angiotensinogen gene with insulin sensitivity in humans: a tagging single nucleotide polymorphism and haplotype approachMetabolism, 2011
- Association of the Angiotensinogen M235T and APO E Gene Polymorphisms in Turkish Type 2 Diabetic Patients with and without NephropathyRenal Failure, 2011
- Renin–angiotensin–aldosterone system genotypes and haplotypes affect the susceptibility to nephropathy in type 2 diabetes patientsJournal of the Renin-Angiotensin-Aldosterone System, 2011
- ACEVariants Interact with the RAS Pathway to Confer Risk and Protection against Type 2 Diabetic NephropathyDNA and Cell Biology, 2009
- Combinational effect of genes for the renin–angiotensin system in conferring susceptibility to diabetic nephropathyJournal of Human Genetics, 2006
- Antidiabetic mechanisms of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonistsJournal of Hypertension, 2004
- Implication of an AGT Haplotype in a Multigene Association Study With Pregnancy HypertensionHypertension, 2004
- Angiotensin I-converting enzyme gene insertion/deletion and angiotensinogen M235T polymorphisms: Risk of chronic renal failureKidney International, 2000
- Angiotensin II stimulates extracellular matrix protein synthesis through induction of transforming growth factor-beta expression in rat glomerular mesangial cells.JCI Insight, 1994
- Molecular basis of human hypertension: Role of angiotensinogenCell, 1992