Gender Based Disparities in ACE I/D Polymorphism Associated with Progression of Diabetic Nephropathy in Pakistani Patients with Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) has become a global problem. Type 2 diabetes mellitus is accelerating pandemic in the Pakistani population as well. The problem progresses with severity of diabetic complications. Diabetic nephropathy (DN) is the most fatal of all these complications. Diabetic nephropathy leads to end stage renal disease if glycemic control and microvascular protection is inadequate. Angiotensin converting enzyme (ACE) gene polymorphism has been reported to be associated with the diabetic nephropathy in type 1 and type 2 diabetes mellitus. ACE plays crucial roles in regulation of rennin angiotensin system. Use of ACE inhibitors and angiotensin receptor blockers (ARBs) can prevent diabetic renal damage. The purpose of this study is to investigate the association of Insertion/deletion (I/D) polymorphism of 287 bp Alu repetitive sequence in intron 16 of ACE gene with diabetic nephropathy. The study includes 284 T2DM Pakistani patients out of which 84 patients developed DN and 108 control subjects. Gender specific ACE gene association was observed in this study. Insertion (I) allele of ACE gene was found to be associated with progression of DN in men with type 2 diabetes mellitus. We did not get any significant association of I allele in women with DN. Neuropathy and family history were strongly associated with progression of diabetic nephropathy. The study will help administer T2DM patients with diabetic nephropathy in Pakistani ethnic groups. Prospective studies need to determine the role of ACE gene I/D polymorphism in Pakistani men with diabetic nephropathy.