To assess the antiproteinuric response to multifactorial treatment based on high doses of angiotensin II receptor antagonists (ARBs) (olmesartan) in patients with non-diabetic proteinuric nephropathies, according to three renin-angiotensin system (RAS) polymorphisms: insertion/deletion of the angiotensin converting enzyme (ACE) gene, the angiotensinogen gene M235T and the angiotensin II type 1 receptor (AT1R) A1166C.
The frequency of T allele, MT/TT genotypes (AGT: M235T), and C allele 1166CC genotype (AGTR1: A1166C) was higher and associated with increased risk of DNP (235T, p < 0.0001; 235TT/MT, p < 0.01; 1166C, p < 0.007; 1166CC, p < 0.0001).
There were no differences in the frequencies of the AGT M235T and ACE I/D genotypes between Turkish patients with type 2 DM with and without nephropathy.
Three SNPs within the AGT, including M235T and one SNP in the AGTR1, were also significantly associated with nephropathy (M235T P=0.01, odds ratio =0.74, 95% CI 0.59-0.94).
The ACE-I/D polymorphism was shown to be a risk factor of progression of renal disease and the AGT-M235T polymorphism was associated with the severity of arterial hypertension.
In this meta-analysis, we attempted to derive pooled estimates for the putative associations between various cardiovascular-renal disorders and the M235T polymorphism of the angiotensinogen gene.
Two variants within the ACE gene (rs4293, P(allelic) =0.02, P(genotypic) =0.008; rs4309, P(allelic) =0.02, P(genotypic) =0.01) were significantly associated with nephropathy at the 5% level.
Two variants within the ACE gene (rs4293, P(allelic) =0.02, P(genotypic) =0.008; rs4309, P(allelic) =0.02, P(genotypic) =0.01) were significantly associated with nephropathy at the 5% level.
We investigated the association of three ACE gene variants with DN, rs1799752 insertion/deletion (I/D), rs1800764T/C and rs12449782A/G in 917 Tunisian type 2 diabetic (T2DM) patients: 515 with (DN) and 402 without (DWN) nephropathy.
In addition, homozygosity for the common haplotype TIC (which corresponded to the T, insertion, and C alleles at the three markers, rs1800764, insertion/deletion, and rs9896208, respectively) versus the CDT/TIC haplotype pair was associated with lower risk for development of persistent microalbuminuria (HR 0.49 [0.32-0.75], P = 0.0009) and severe nephropathy (0.41 [0.22-0.78], P = 0.006).