Association of the receptor for advanced glycation end products (RAGE) -374 T/A gene polymorphism and circulating soluble RAGE with nephropathy in type 1 diabetic patients.

The binding of advanced glycation end-products (AGEs) to their receptor (RAGE) may play an important role in the development of diabetic vascular complications. Circulating soluble RAGE (sRAGE) reflects tissue RAGE expression. We examined circulating sRAGE and RAGE -374 T/A gene promoter polymorphism in type 1 diabetic patients and explored their possible associations with the development of nephropathy. Fifty diabetic patients with disease duration >10 years and 20 age, sex and body mass index (BMI) matched healthy controls were included in the study. Diabetic patients were subdivided into 23 patients without nephropathy and 27 with nephropathy. All the studied individuals were subjected to the following investigations: fasting glucose, HbA1c, serum creatinine, lipid profile, albuminuria and sRAGE levels. The -374 T/A RAGE gene polymorphism was studied by PCR amplification and restriction fragment length polymorphism (RFLP) analysis. Our study reported significant increase in sRAGE in diabetic patients compared to controls and in diabetic patients with nephropathy compared to those without nephropathy (P < 0.001). sRAGE was significantly correlated with HbA1c, creatinine, albuminuria and atherogenic lipid profile. There were significant increase in the frequency of RAGE -374 A allele (T/A and/or A/A genotypes) in diabetic patients with nephropathy compared to those without nephropathy and control groups (P < 0.01). A allele was a risk factor for diabetic nephropathy (OR 2.36 & 95% CI 1.1-5.6). RAGE -374 A allele was associated with increased sRAGE levels, hypertension and increased creatinine concentration in diabetic patients. This study points to the possible role of sRAGE as a marker of early nephropathy in diabetic patients. Early testing for the RAGE gene -374 T/A could have merit in predicting risk of diabetic nephropathy later in life.