Association between genetic polymorphisms of ACE & eNOS and diabetic nephropathy

Abstract

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, with multiple genetic and environmental factors involving in its etiology. ACE and eNOS gene were considered to have important roles in the development and progression of DN. In this study, a case-control study was carried out to investigate the effects of 7 SNPs in ACE gene and 2 SNPs in eNOS gene in the development of DN in Northern China.7 SNPs including A240T, A2350G, A5466C, A2215G, T3892C, C1237T and C3409T of ACE gene and 2 SNPs (G894T and T786C) of eNOS gene were genotyped by polymerase chain reaction restriction fragment length polymorphism method. 431 type 2 diabetic patients with nephropathy (cases) were compared to 420 type 2 diabetic patients without nephropathy (controls) in the study. Data were analyzed by SPSS 17.0 and HaploView software. The frequency distribution of A2350G, 4 haplotyps in ACE gene and G894T in eNOS gene were demonstrated to be different between case and control groups significantly. Whereas other SNPs and haplotypes had no differences in two cohorts. The results revealed that variations of ACE and eNOS gene had association with DN, which indicated ACE and eNOS gene may play an important role in pathogenesis of DN in Northern Chinese Han population.

Association between nitric oxide synthase T-786C genetic polymorphism and chronic kidney disease: Meta-analysis incorporating trial sequential analysis

“…This case-control study did not find any significant relationships between T-786C and ESRD risk. This result is consistent with the findings of some previous studies [ 20 , 21 ]. However, other studies have highlighted that T-786C is associated with ESRD risk [ 30 , 31 ].…”

“…The latest meta-analysis article was published in 2015 and included 4203 subjects. However, many new case-control studies are still excluded in that meta-analysis [ 19 – 21 ]. Additionally, previous meta-analyses were unable to prove if a definite conclusion can be ascertained from the correlation between eNOS T-786C and CKD [ 22 ].…”

Farnesoid X Receptor Agonism Protects against Diabetic Tubulopathy: Potential Add-On Therapy for Diabetic Nephropathy

“…19 In addition, DDAH1 inhibits asymmetric dimethylarginine and N g -monomethyl-L-arginine, two inhibitors of nitric oxide synthase and hence of nitric oxide production. 20 As eNOS deficiency markedly aggravates dNP in mice 21 and is suggested to contribute to dNP in humans, 22 induction of DDAH1 via FXR may endow TUDCA with additional FXRdependent renoprotective effects in dNP ( Figure 4G). Accordingly, TUDCA may protect from dNP not only by ameliorating maladaptive ER signaling, but additionally by targeting FXR-or TGR5-dependent pathophysiologic mechanisms.…”

Correlation of Endothelial Nitric Oxide Synthase Gene Polymorphism (GG, TT and GT Genotype) with Proteinuria and Retinopathy in Type 2 Diabetic Patients

“…Bernhard et al, in their study on type 1 and type 2 diabetic patients did not find that eNOS gene polymorphism plays a significant role in the development of diabetic nephropathy [24]. Huo P in Chinese population found an association between ACE and eNOS and diabetic nephropathy [25]. Rahimi in a study on 173 diabetic patients and 101 healthy cases found the significantly increasing risk of macroalbuminuria in the presence of either eNOS 4a or 894T allele, however, he could not find any association between concomitant presence of both alleles with increasing risk of macroalbuminuria [26].…”