Prognostic Significance of ACE and PAI-1 Genes Polymorphisms with Diabetic Retinopathy and Diabetic Non-Retinopathy in Type 2 Diabetes.

ABSTRACT

Background: ACE a renin-angiotensin system that regulates blood pressure, balance of fluids and salts in body and PAI-1 is a serine protease inhibitor, which inhibits tissue plasminogen activator andurokinase.They are thought to play an important role in pathophysiology of kidney disease in diabetes. Aim: In our present study, we studied the association of altered ACE-gene and PAI-1 gene with diabetic retinopathy (DR) and NDR in 592 samples consisted of (cohort I; 196 DR patients, cohort II; 200 diabetic nonretinopathy (DNR) and cohort III, 196 respective controls. Methods: For genotyping of ACE-gene and PAI-1 gene, genomic DNA was isolated and purified which was then amplified by PCR, and thePCR products analyzedwere by Agarose gel electrophoresis. Results: In first part, the ACE genotype and allele frequency distribution was studied. For ACE gene polymorphism, the genotype and allele frequency distribution were analyzed in DR subjects and respective controls. The results indicated that there is no statistically significant difference between DR males and females compared to respective controls. The results were significantly high between genotype frequencies of DR and DNR in males. The recessive model was found to be significantly associated with the DR male subjects (OR=0.45 [95% CI=0.20-0.99], p<0.05), whereas in females these are non-significant as compared to respective controls individuals. In second part of study, the disease status analysis of ACE gene on basis of DR stages (NPDR and PDR) was observed. The χ2 analysis indicated that results are significantly different between NPDR and respective controls (χ2=8.75, p=0.01) .And in third part of present study, disease status analysis for PAI-1 gene on the basis of DR stages (NPDR and PDR) was studied, which indicated statistically nonsignificance. The χ2 analysis values for DNR and NPDR and for DNR and PDR was (χ2=0.48, p>0.05)(χ2 =2.00, p>0.05) respectively, Conclusion: Our present study suggests that changes in genetic polymorphisms of ACE-gene and PAI-1 gene in DR, DNR and T2D Patients are risk factors, which may serve as useful prognostic markers.