OP-11：Is there inter-ethnic variation in genetic usceptibility to diabetic nephropathy?

Daniel P K Ng^1,2, Tai Bee Choo^2,1, David Koh^1,2, Tan Kar Wai², Chia Kee Seng^1,2

¹Department of Community, Occupational and Family Medicine, National University of Singapore

²Centre for Molecular Epidemiology, National University of Singapore

Genetic susceptibility for diabetic nephropathy, as seen by familial clustering, has been demonstrated in diverse human ethnic groups. However, it is unclear whether the same genes act as common risk factors across these different groups of patients. While very few genes have been extensively studied to allow this important question to be answered, one possible exception is the ACE gene on human chromosome 17q23. This gene encodes for angiotensin-I converting enzyme that forms an integral part of the renin-angiotensin system responsible for blood pressure regulation and regional blood flow. A survey of literature published to date revealed nearly 50 distinct studies that have examined the association of the ACE insertion/deletion polymorphism with risk of diabetic nephropathy. Using cases defined on the minimal criterion of microalbuminuria and controls on the basis of normoalbuminuria, our meta-analysis showed that the genetic risk associated with this marker was significantly higher among type 2 diabetic Asians (including Chinese, Japanese, and Koreans) compared to Caucasians with type 2 diabetes (P < 0.019). We conclude that genetic susceptibility for diabetic nephropathy ascribed to a particular gene locus (e.g. ACE) can vary substantially among different ethnic groups. Our present findings thus emphasize the need for population-specific studies especially in Asia to facilitate the identification of susceptibility genes for this serious complication.