Association between Angiotensin-converting Enzyme Gene Insertion/Deletion Polymorphism with Diabetic Peripheral Neuropathy and Its Importance as a Genetic Biomarker

Abstract

Background: Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of type 2 diabetes mellitus (T2DM) with a prevalence ranging from 18.8% to 61.9% in India. For patients with T2DM, identifying those who are at risk of developing DPN is crucial for planning and implementing secondary preventive interventions, as well as for stepping up efforts to address risk factors. Very few studies have discovered a connection between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms and the onset and progression of DPN in T2DM. Objectives: The current study intends to investigate the relationship between ACE gene I/D polymorphism with T2DM and DPN subjects among the South Tamil Nadu regional population. Materials and Methods: Thirty T2DM patients with DPN, 30 T2DM patients without DPN, and 30 control (nondiabetic) subjects were enrolled in this study. DPN was diagnosed using clinical and neurophysiological evaluation. Blood samples were collected and subjected to relevant investigations including blood glucose, glycated hemoglobin, serum creatinine, and serum lipids. Polymerase chain reaction amplification was performed to genotype the DNA for ACE I/D polymorphism using specific primers. Results: The ACE genotypes were distributed as II, 17 (57%); DD, 3 (10%); and ID, 10 (33%) in control group; II, 7 (23%); DD, 11 (37%); and ID, 12 (40%) in T2DM without DPN group, II, 3 (10%); DD, 16 (53%); and ID, 11 (37%) in T2DM with DPN group. The frequency of DD genotype was significantly higher in T2DM (P = 0.03) and T2DM patients with DPN (P = 0.001) compared to controls. The DD genotype versus II genotype was found to be associated with an increased risk of DPN (odds ratio [OR] = 10.28; 95% confidence interval [CI] =2.55–41.37). The D allele was more frequent among T2DM patients with DPN (71.6%) followed by T2DM patients (56.6%) compared to controls (26.6%). The D allele (vs. the I allele) is associated with an increased risk of T2DM (OR = 3.59, 95% CI = 1.670–7.742) and DPN (OR = 6.95, 95% CI = 3.120–15.507). Conclusion: The D allele and DD genotype of the ACE gene may both be risk factors for T2DM; in fact, the D allele of this polymorphism may potentially be linked to the development of DPN in T2DM patients. This finding implies that it may be possible to prevent DPN by early detection by identifying defects in ACE I/D polymorphisms in the south Indian regional population.