Journal Article

Lack of relationship in long‐term type 1 diabetic patients between diabetic nephropathy and polymorphisms in apolipoprotein <i>ε</i>, lipoprotein lipase and cholesteryl ester transfer protein

Samy Hadjadj, Yves Gallois, Gilles Simard, Béatrice Bouhanick, Philippe Passa, André Grimaldi, Pierre Drouin, Jean Tichet and Michel Marre

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 15, issue 12, pages 1971-1976
Published in print December 2000 | ISSN: 0931-0509
Published online December 2000 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/15.12.1971
Lack of relationship in long‐term type 1 diabetic patients between diabetic nephropathy and polymorphisms in apolipoprotein ε, lipoprotein lipase and cholesteryl ester transfer protein

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Background. Genetic susceptibility contributes to the risk of diabetic nephropathy. Lipid disorders may favour diabetic nephropathy. Thus polymorphisms in lipid metabolism are candidates for the genetic component of risk for diabetic nephropathy.

Methods. We searched for a contribution of the genetic polymorphisms of lipoprotein lipase (LPL), cholesteryl ester transfer protein (CETP) and apolipoprotein ε (Apo E) to the development of diabetic nephropathy by studying 494 type 1 diabetic patients with proliferative retinopathy and various stages of diabetic nephropathy (GENEDIAB Study). The selection process ensured that all patients had expressed their risk of chronic complications due to uncontrolled diabetes. Thus the nephropathy stages were largely influenced by genetic background. The lipid profile included fasting plasma total cholesterol (TC), triglycerides (TG), apolipoprotein A1 (Apo A1) and B (Apo B), and lipoprotein (a) (Lp(a)). Genetic polymorphisms were determined by PCR‐based detection of Apo ε (e2/e3/e4), LPL (mutation Asn 291 Ser) and CETP (TaqIB B1/B2).

Results. One hundred and fifty‐seven patients (32%) had no nephropathy, 104 (21%) incipient nephropathy, 126 (25%) established nephropathy and 107 (22%) advanced nephropathy. There was a significant relationship between the stages of diabetic nephropathy and TC (P=0.002), TG (P<0.0001), Apo B (P=0.0007) or Lp(a) (P=0.038), but not Apo A1. However the genetic polymorphism distributions of LPL, CETP and Apo ε did not differ in terms of renal complications. The study power to reject the null hypothesis was 58% for the Apo ε genotypes.

Conclusion. These results support no or only marginal effects of a genetic basis for lipid disturbances encountered in diabetic nephropathy.

Keywords: apolipoprotein E; cholesteryl ester transfer protein; diabetic nephropathy; genetics; lipoprotein lipase; type 1 diabetes

Journal Article.  3735 words. 

Subjects: Nephrology

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