Genetic Variation in the Renin-Angiotensin System and Diabetic Nephropathy in the Tunisian Population

The aim of this study was to evaluate the association of ACE, angiotensinogen (AGT) and angiotensin II receptor type I (AGTR1) polymorphisms with diabetic nephropathy (DN) in Tunisians.

The study population comprised 236 type 2 diabetic patients: with nephropathy (DN = 47) and without nephropathy (DM = 189). Genotyping of ACE-I/D-rs1799752, ACE-rs4343G>A, AGT-rs5050A>C, AGT-rs 4762C>T, AGT-rs699A>G, and AGTR1-rs5186A>C was performed by PCR-RFLP. Haplotype and statistical analysis were realized using SNP Analyzer2.0 and SPSS20, respectively.

Genotype frequencies were in Hardy-Weinberg equilibrium. After adjustment for potential confounding factors (age, gender, diabetes duration, hypertension…), an increased risk for DN was associated with mutated alleles of rs4762 (OR = 10.25, p = 0.001), rs699 (OR = 22.21, p < 0.001), and rs5186 (OR = 11.25, p < 0.001). However, mutated alleles of rs1799752 seemed to be protector (OR = 0.41, p = 0.011). Adjusted ORs of DN associated with the ACE haplotype (DA) was (OR = 9.56, p = 0.047) and with the ACE-AGT haplotype (ATADAA) was (OR = 5.38, p = 0.032).

This study indicates that common variants in ACE, AGT, and AGTR1 seem to play a role in genetic susceptibility to DN in Tunisian population and provides evidence for a disease haplotype: ATADAA.