Acetylation Pharmacogenetics and Renal Function in Diabetes Mellitus Patients

摘要

Activities of human hepatic drug metabolizing enzymes N-acetyl transferase (NATS) had earlier been recognized as a cause of inter-individual variation in the metabolism of drugs. Therefore acetylation of many drags in human exhibit genetic polymorphism. The aim of the study was to investigate if acetylator status predispose diabetic mellitus patients more to the complications of renal disease, One hundred and twenty (120) diabetics consisting of (50) Type 1 (T_1) and 70 Type 2 (T_2) diabetes mellitus patients and 100 healthy individuals as controls were classified as slow or rapid acetylator using sulpha-methazine (SMZ) as an in vivo probe. The percentage acetylation, recovery of SMZ, creatinine clearance and presence of urinary albumin were determined. A significant difference (P < 0.05) was observed in the percentage of SMZ acetylated between slow and rapid acetylators in control, T_1 and T_2 subjects. The ratios of slow to rapid acetylators for T_1 T_2 and control subjects were 1:4, 3:2 and 2:3 respectively. No significant differences were observed in the percentage of SMZ recovered in the urine of slow and rapid acetylators that are diabetics. The difference in creatinine clearance of slow and rapid acetylators in T_1 and T_2 were significant (P < 0.05). 29% out of 120 (24.2%) diabetics (T_1 and T_2) exhibited albuminuria out of which 25 (86.2%) had slow acetylator status. These findings suggest that slow acetylator status in diabetes mellitus could be a predisposing factor in the development of renal complications. This underscores the need for a rapid pharmacogenetic testing and therapeutic drug monitoring in such patients. However this inference could be further validated with a larger sample size.