Abstract
The AKR1B1 gene encodes an enzyme that catalyzes the reduction of glucose into sorbitol. Chronic hyperglycemia in patients with diabetes mellitus (DM) leads to increased AKR1B1 affinity for glucose and, consequently, sorbitol accumulation. Elevated sorbitol increases oxidative stress, which is one of the main pathways related to chronic complications of diabetes, including diabetic kidney disease (DKD). Accordingly, some studies have suggested the rs759853 polymorphism in the AKR1B1 gene is associated with DKD; however, findings are still contradictory. The aim was to investigate the association of the rs759853 polymorphism in the AKR1B1 gene and DKD. The sample comprised 695 patients with type 2 DM (T2DM) and DKD (cases) and 310 patients with T2DM of more than 10 years' duration, but no DKD (controls). The polymorphism was genotyped by real-time PCR. Allelic and genotype frequencies of this polymorphism did not differ significantly between groups. However, the A/A genotype was associated with risk for DKD after adjustment for gender, triglycerides, BMI, presence of hypertension and diabetic retinopathy, and duration of DM, under both recessive (P = 0.048) and additive (P = 0.037) inheritance models. Our data suggest an association between the AKR1B1 rs759853A/A genotype and risk for DKD in Brazilians T2DM patients.
Highlights
Diabetic kidney disease (DKD) is an important microvascular complication that affects around 40% of all patients with diabetes mellitus (DM), and is the leading cause of end-stage renal disease in individuals on renal replacement therapy
AKR1B1 acts on the polyol pathway by catalyzing the reduction of glucose to sorbitol
This pathway leads to intracellular buildup of sorbitol, causing tissue damage – as observed in the microvascular complications of diabetes, including DKD [24]
Summary
Diabetic kidney disease (DKD) is an important microvascular complication that affects around 40% of all patients with diabetes mellitus (DM), and is the leading cause of end-stage renal disease in individuals on renal replacement therapy. Aldo-keto reductase family 1 member B (AKR1B1), known as aldose reductase, belongs to the aldo/ keto reductase superfamily and is the first enzyme of the polyol pathway, catalyzing the reduction of glucose into sorbitol using NADPH as a cofactor [reviewed in [5,6]]. This reaction is the rate-limiting step of the polyol pathway.
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