The Challenging Search for Diabetic Nephropathy Genes

  1. Barry I. Freedman2
  1. 1Department of Biochemistry, Centers for Diabetes Research and Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Wake Forest University, Winston-Salem, North Carolina
  2. 2Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Wake Forest University, Winston-Salem, North Carolina
  1. Corresponding author: Donald W. Bowden, dbowden{at}wfubmc.edu.

It is widely appreciated that macro- and microvascular complications, rather than hyperglycemia per se, are major contributors to morbidity and mortality in diabetes. In this issue of Diabetes, Williams et al. (1) report the results of a meta-analysis of genetic data from three moderately sized studies of patients with type 1 diabetes (T1D) and nephropathy. This report illustrates several challenges inherent in the genetic analysis of diabetes complications and is another step toward understanding the genetic basis of risk for diabetic nephropathy (DN). Insights into the genetics of DN will potentially lead to improved prediction of DN and novel approaches to prevent this serious complication of diabetes.

There is compelling evidence in support of a major genetic component for diabetes complications, especially DN. Efforts to identify genes contributing to T1D and type 2 diabetes (T2D) have been highly successful, but with few exceptions, there is little evidence that diabetes-associated variants associate with complications. Thus, diabetes complications appear to have an independent genetic basis. The profound public health impact of DN has motivated the performance of multiple genetic studies. However, these studies are complicated by issues of disease origin (T1D or T2D), ethnicity (European and European American, African American, Hispanic, Asian), competing cardiovascular risk, and variable diagnostic criteria (glomerular filtration rate and albuminuria in mildly affected individuals, variable severity of chronic kidney disease or end-stage renal disease [ESRD] requiring renal replacement therapy). Consequently, existing genetic association studies of DN have included a …

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