Significant association of candidate genes (AGTR1 and TGF-β1) polymorphism with diabetic nephropathy in diabetes mellitus type 2 patients

Abstract

Abstract Background Diabetic Nephropathy (DN) is one of the microvascular complications of Diabetes Mellitus (DM). Genome wide association studies have helped identify gene variants such as rs1800470 (TGF-β1) and rs5186 (AGTR1), which facilitate diabetic nephropathy. However, there is no such reports from Pakistan, particularly the Pashtun population. Methods A case-control study was conducted on 165 diabetic patients (59 with Diabetic Nephropathy (DN) and 54 without DN (DM)), and 52 healthy subjects (HC). The genotyping was done using amplification refractory mutation system method (ARMS-PCR). Results The results indicated that all the subjects have similar distribution of age, gender and duration of diabetes, while the FBS, RBS, HbA1C, creatinine, Urea, SBP, DBP, total cholesterol, triglycerides, LDL and BMI were found higher in the diabetic patients with nephropathy as compared to those without nephropathy and healthy controls. The risk allele of AGTR1, C (p < 0.0001), and risk allele containing genotypes AC (p < 0.0001) and CC (p- 0.0010) were significantly higher in DN patients compared to DM and HC groups. Similarly, the TGF-β1 risk allele C (p- 0.0001), and corresponding genotypes TC (p- 0.0038) and CC (p- 0.0027) were significantly associated with increased risk of diabetic nephropathy compared to DM and HC groups. Conclusion The data showed significant association of AGTR1 (rs5186) and TGF-β1 (rs1800470) polymorphism with an increased risk of diabetic nephropathy in type 2 diabetes mellitus patients. More investigation will be required to disseminate the results, while increasing the samples size and using whole genome sequencing.