Pharmacogenomic Studies of ACE and ARB Inhibitor Drug Therapy in Type-II Diabetic Nephropathy (T2DN) Patients with GSTT1 and GSTM1 Gene Polymorphisms

ABSTRACT

Background and Objective: Diabetic nephropathy is one of the most common and serious complications of diabetes mellitus with pathological activation of Rennin Angiotensin Aldosterone System (RAAS) as the key pathogenic mechanism. The purpose of the present study was to investigate the pharmacogenomic involvement and genetic polymorphism of GSTT1 and GSTM1 genes in Type-II Diabetic Nephropathy (T2DN) patients taking ACE or ARB inhibitor drugs in Hyderabad Indian population. The Renin-Angotensin-Aldosterone System (RAAS) includes angiotensin converting enzymes-ACE-inhibitors and angiotensin -receptor blockers- ARBS, these are widely used in treatment of DN. Materials and Methods: This study was a case control study conducted on 40 T2DN patients taking ARB or ACE inhibitor drugs and 40 controls of Hyderabad population of India. The cases were reporting to hospital for checkup. Institutional Ethics Committee approved the conduct of this study. Patient=s demographs were collected by direct interview. Blood samples were collected for GST genotyping by multiplex PCR-based methods. Results: It was observed that GSTT1 gene polymorphism was associated with the risk of developing T2DN (p= 0.01) taking ARB or ACE inhibitor drug, but there was no clear evidence that GSTT1 gene was directly involved in pharmacogenomic drug response in treated T2DN patients. Whereas GSTM1 gene polymorphism was associated neither with the risk of developing T2DN (taking ARB or ACE inhibitor drug) nor any clear evidence that GSTM1 gene was involved in pharmacogenomic drug response in treated T2DN patients. Understanding the biological differences in the activity of GSTT1 relative to GSTM1 helps to identify pathways involved in DN. Conclusion: GSTT1 gene polymorphism appears to contribute to the development of T2DN in Hyderabad population. However the involvement of these detoxifying genes (GSTs) in the pharmacogenomic drug response in diabetic nephropathy patients (taking ARB or ACE inhibitor drugs) was not clearly understood due to the patient heterogeneity. This is a preliminary study which give us the lead to further investigate the role of these genes with reference to the two popular drugs ARB and ACE inhibitors, these findings will be confirmed with larger number of samples.