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

Abstract

Background:Aldose reductase (AR) is the rate-limiting enzyme in the glucose metabolism, which has been implicated in the pathogenesis of diabetic microvascular complications (MVCs). Frequent C-106T polymorphism in the promoter of the AR gene may change the expression of the gene.Aims:The aim of the following study is to study the association between AR C106T genotypes and diabetic MVCs in Iranian population.Materials and Methods:We included 206 type 2 diabetic patients categorized into two groups according to the presence or absence of diabetic microangiopathy. The cases of interest were diabetic neuropathy, retinopathy and nephropathy identified during clinical and or laboratory examination. In addition, 114 age- and sex-matched individuals were selected to serve as a control group. AR genotyping was done using an amplification gel electrophoresis.Results:The frequency of CC genotype was specifically higher in subjects with diabetic retinopathy as compared to those without it (53.2% vs. 38.1%, P = 0.030). Patients with diabetic microangiopathy in general; however, did not differ significantly between AR genotype groups.Conclusion:The C-106T polymorphism in the AR gene is likely a risk factor for development of only retinal complication of diabetes microvascular in Iranian individuals.

Update on genetics and diabetic retinopathy

“…AR converts glucose to sorbitol in the polyol pathway; 14 sorbitol cannot cross cell membranes but can accumulate in insulin-independent tissues, where it draws in water and produces osmotic stress. 15 Multiple studies have reported conflicting results regarding a potential association between AKR1B1 and DR. 16 – 26 For example, the C(−106)T polymorphism was significantly associated with DR in a series of 206 Iranian patients with type 2 diabetes ( P =0.03) 27 but not in a series of 268 Chinese patients with type 2 diabetes. 28 A meta-analysis of 7,831 patients from 17 studies from Asia, South America, Europe, and Australia reported a significant association between the C(−106)T polymorphism and DR in patients with type 1 diabetes (odds ratio [OR] =1.78, 95% confidence interval [CI] =1.39–2.28) but not type 2.…”

The relationship between aldose reductase gene C106T polymorphism and the severity of retinopathy in Type 2 diabetic patients: A case–control study

“…An Iranian study showed that the C106T polymorphism in the ALR2 gene is a potential risk factor for the development of a retinal microvascular complication of diabetes in their population. [ 6 ] Studies on English population demonstrated the same association but in Type 1 diabetic patients. [ 5 ] Studies on Chinese patients with Type 2 diabetes showed both a significant and a nonsignificant association of C106T polymorphism of the ALR2 gene with retinopathy.…”

“…[ 1 2 ] Poor glycemic control affects both the development and progression of diabetic retinopathy (DR). [ 3 ] Family history of genetic polymorphisms in several genes including aldose reductase gene (ALR2) increases diabetic complications risk suggesting that genetic factors may also play a role in the pathogenesis of DR.[ 4 5 6 7 ]…”

Aldose reductase (-106) C/T gene polymorphism and possibility of macrovascular complications in Egyptian type 2 diabetic patients

“…Some studies suggested that high-glucose flux via AR pathway in hyperglycemia triggers alteration of glucose metabolism,[ 37 ] and vascular perturbation, leading to prothrombotic and pro-inflammatory responses in diabetic atherosclerosis,[ 38 ] and high AR expression in mice accelerates diabetic atherosclerosis both globally and in endothelial cells. [ 39 ] Results from various cellular and animal models representing a number of inflammatory conditions suggested that inflammation induced by oxidative stress which is a major contributor to diabetic complications could be reduced by the inhibition of AR which can be used for future treatment.…”