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

Abstract

Introduction:Over the past three decades, the number of people with diabetes mellitus (DM) has more than doubled globally, making it one of the most important public health challenges to all nations. Aldose reductase (AR) is a rate-limiting enzyme in the polyol pathway, which has been implicated in the pathogenesis of diabetic microvascular complications; however, the association of the AR gene with diabetic macrovascular complications has rarely been investigated.Aim:The study aimed to identify the possible association between C(-106) T polymorphism of the AR gene and diabetic macroangiopathy in a cohort of Egyptian patients with type 2 DM.Settings and Design:This study was conducted on 100 Egyptian subjects, the control group (n = 20) and the patient group (n = 80) with type 2 diabetes which were further subdivided into two subgroups with (n = 48) and without macroangiopathic complications (n = 32) as evidenced by carotid intima-media thickness, electrocardiography (ECG) ischemic changes, cerebrovascular insufficiency, and peripheral vascular insufficiency.Subjects and Methods:All studied subjects were subjected to detailed history taking, clinical examination, ECG, carotid ultrasonography, routine laboratory investigations, and molecular studies including the detection of AR C(-106) T gene polymorphisms using the polymerase chain reaction (PCR)/restriction fragment length polymorphism technique.Results:The genotype distribution and allele frequency of AR C(-106) T showed no statistical significance also the genotypes were not associated with any of the different studied parameters.Conclusions:The results suggest that the C(-106) T polymorphism in the AR gene is not involved in the pathogenesis of macroangiopathy in type 2 diabetes.

Genetic Polymorphisms of Antioxidant and Antiglycation Enzymes and Diabetic Complications. How Much Can we Learn from the Genes?

“…A study from 2004 in Finland suggested that the C-106T polymorphism of the aldose reductase gene could be involved in the early development of microalbuminuria in Finnish type 2 diabetic patients [49]. A study on an Egyptian cohort showed, that the C(-106) T polymorphism in the AR gene is not involved in the pathogenesis of macroangiopathy in type 2 diabetes [50]. In contrast, another study found a statistically significant association of AKR1B1 -106C > T polymorphism with retinopathy in North Indian patients [51].…”

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

“…[ 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. [ 12 17 ] A study on Egyptians, Australians, and Indonesians of Yogyakarta did not show the association between C106T polymorphism and DR.[ 18 19 20 ] In a meta-analysis of studies performed on Chinese population, the overall analysis demonstrated a nonsignificant association between the ALR2 C106T polymorphism and DR, whereas, subgroups stratified by ethnicity analyzed in this study showed significantly increased risks for DR in ALR2 C106T variants of the Chinese Han population. [ 21 ] Another meta-analysis that involved 3512 diabetic patients with DR and 4319 diabetic patients without it found that ALR2 C106T polymorphism was not associated with a higher risk to develop DR, however, ALR2 C106T polymorphism increased the risk of DR in Type 1 diabetic patients but not in Type 2 diabetics.…”

Polymorphisms in Sorbitol-Aldose Reductase (Polyol) Pathway Genes and Their Influence on Risk of Diabetic Retinopathy Among Han Chinese

“…Genotyping was performed on DNA isolated from the blood specimens. For ALR2 rs759853 polymorphism, genotyping was performed through direct bidirectional sequencing with BigDye Terminator v3.1 Cycle Sequencing Kit (Thermo Fisher Scientific, Massachusetts, USA), by using the primers 5′-CCT TTC TGC CAC GCG GGG CGC GGG-3′ (forward) and 5′-CAT GGC TGC TGC GCT CCC CAG-3′ (reverse) [10]. For SDH rs2055858 and rs3759890 polymorphisms, genotyping was performed with PCR-based method as described [11].…”