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(Hypertension. 2006;48:8.)
© 2006 American Heart Association, Inc.

Brief Reviews

Genetic Susceptibility Contributes to Renal and Cardiovascular Complications of Type 2 Diabetes Mellitus

Barry I. Freedman; Donald W. Bowden; Michèle M. Sale; Carl D. Langefeld; Stephen S. Rich

From the Department of Internal Medicine (B.I.F., D.W.B., M.M.S.), Department of Biochemistry (D.W.B.), Center for Human Genomics (D.W.B., M.M.S.), and Division of Public Health Sciences (C.D.L., S.S.R.), Wake Forest University School of Medicine, Winston-Salem, NC.

Correspondence to Barry I. Freedman, Section on Nephrology, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1053. E-mail bfreedma@wfubmc.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
More than 100 000 Americans were diagnosed with end-stage renal disease (ESRD) and initiated renal replacement therapy in 2003. Diabetes mellitus (DM) was the etiology of ESRD in nearly one half (44.2%) of these incident cases. Overall, 324 826 Americans received renal replacement therapy in 2003 at a cost of more than $27.3 billion.¹ Diabetic subjects are not at equal risk for developing progressive diabetic nephropathy (DN).² Diabetic blacks have a 4-fold higher incidence rate of ESRD compared with whites.¹

Familial aggregation of albuminuria, DN, and ESRD have long been observed.^3,4 The magnitude of familial aggregation of ESRD was demonstrated in a study of 25 883 incident dialysis patients.⁵ After exclusion of cases with monogenic genetic kidney diseases (ie, autosomal dominant polycystic kidney disease and hereditary nephritis), almost one quarter (22.8%) of incident dialysis patients (31.6% of black women and 27.5% of black men) reported having a first-degree and/or second-degree relative with ESRD. Multivariate analysis revealed that diabetes-associated ESRD, black ethnicity, and younger age at ESRD were significant and independent predictors of familial aggregation of ESRD. A population-based cohort study⁶ further demonstrated that the familial clustering of DN was in excess of that which could be explained by an excessive prevalence of diabetes and hypertension in families. Together, these reports suggest the presence of "renal failure susceptibility genes," independent from genetic factors causing type 2 diabetes per se.

	Genetic Factors in DN

 
Many studies have evaluated the roles of specific "candidate genes" in susceptibility to DM-ESRD and DN. The results of these candidate gene . . . [Full Text of this Article]

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