C-106T Polymorphism in Promoter of Aldose Reductase Gene Is a Risk Factor for Diabetic Nephropathy in Type 2 Diabetes Patients with Poor Glycaemic Control

Abstract

Background: Excessive flux through the polyol pathway has long been thought to be involved in the pathogenesis of diabetic microvascular complications. Aldose reductase (AR) is the first and rate-limiting enzyme in the pathway that catalyses the reduction of glucose to sorbitol. A frequent C-106T polymorphism in the promoter of the AR gene has been described, which may change the expression of the gene. The aim of the study was to examine if the C-106T polymorphism was associated with diabetic nephropathy. Material and Methods: We collected 444 patients with type 2 diabetes and divided them into three groups according to the renal status: 162 patients with normoalbuminuria, 153 with microalbuminuria and 129 with persistent proteinuria. Each subject was genotyped for the C-106 polymorphism using the PCR-based RFLP protocol. Results: When the whole study population was analysed, no distortion in the genotype frequency among the study groups was observed. When we stratified the study population by HbA1c we found that in patients with HbA1c ≧9% (median) the CT and TT genotypes were more frequent in patients with diabetic nephropathy (proteinuria and microalbuminuria) than those with normoalbuminuria (OR 2.04, 95% CI 1.12–3.74). Conclusion: The C-106T polymorphism in the AR gene is a risk factor for development of diabetic nephropathy in type 2 diabetes in patients with poor glycaemic control.

Association of genetic variants with diabetic nephropathy

“…This polymorphism in aldose reductase gene was also found to be associated with nephropathy in type 1 and type 2 diabetic patients [54] . This polymorphism was also found to be involved in the early development of microalbuminuria in Finnish T2DM patients and was proposed as a risk factor for development of nephropathy in T2DM patients with poor glycaemic control [55] . Glucose transporter 1: Glucose transporter 1 (GLUT1 or SLC2A1) is the major facilitative glucose transporter in glomerular mesangial cells.…”

Molecular Genetic Approaches for Studying the Etiology of Diabetic Nephropathy

“…An (AC)n microsatellite polymorphism, located 2.1 kb upstream of AKR1B1, was initially reported to be associated with early onset retinopathy in Chinese type 2 diabetic patients [80]. Subsequent studies investigating whether this marker is associated with DN have yielded mixed results [79,[81][82][83][84][85][86][87][88]. NeatmatAllah et al undertook a small meta-analysis of the ( A C ) n marker and found no evidence for an association between the putative Z-2 allele and DN in five studies on type 2 diabetic patients [87].…”

Aldose reductase C-106T gene polymorphism in type 2 diabetics with microangiopathy in Iranian individuals

“…However, the association between the T allele of the C-106T polymorphism and the prevalence of gross albuminuria was not observed in many studies. [ 25 34 35 ] In some studies, no association between the polymorphisms and the risk of retinopathy were observed,[ 36 37 ] which is in contrast with other reports from type 2 diabetic patients. [ 22 38 39 40 ] Diabetic patients with the T allele of the C-106T polymorphism of the AR gene had lower sensory response amplitudes and in cases with longer duration, a greater decrease in NCV of the motor nerve than the subjects with the C-106C genotype.…”