Null association between ACE gene I/D polymorphism and diabetic nephropathy among multiethnic Malaysian subjects

Background: Wide inter-ethnic allelic variations of the Angiotensin Converting Enzyme (ACE) i nsertion-deletion (I/D) gene polymorphism were thought to be responsible for the conflicting gene-diabetic nephropathy disease association worldwide. We have investigated the genetic susceptibility of the ACE gene to diabetic nephropathy in the multiethnic Malaysian population. Materials and Methods: A total of 137 healthy (control) and 256 diabetic subjects were recruited. The diabetic subjects were further subdivided according to their nephropathy status based on urinary albumin-creatinine ratio (ACR) and glomerular filtration rate (GFR). Triple primer polymerase chain reaction (PCR) was used for ACE I/D genotyping. Subsequently, populationwide genetic analysis and gene-disease association studies were performed. Results: The genotype frequencies in all subgroups were in Hardy-Weinberg equilibrium. Similar allelic and genotypic frequency of ACE I/D gene polymorphism was observed between healthy controls versus pooled type 2 diabetes mellitus (T2DM) subjects, and normoalbuminuria versus microalbuminuria, macroalbuminuria and End Stage Renal Failure (ESRF) (P > 0.05). Neither ethnicity nor gender exerted any influence on the ACE I/D gene polymorphism (P > 0.05), with the exception of the Chinese ethnic group which exhibited a higher frequency of ID genotype (P = 0.042). A multinomial logistic regression model showed that predictive factors including age, systolic blood pressure (SBP), high density lipoprotein (HDL) and glycosylated hemoglobin (HbA1C) were independently associated with diabetic nephropathy, in that order. Conclusion: The I/D polymorphism of the ACE gene is not significantly associated with both T2DM and/or diabetic nephropathy in this Malaysian population regardless of ethnicity and gender