Lack of relationship in long-term type 1 diabetic patients between diabetic nephropathy and polymorphisms in apolipoprotein epsilon, lipoprotein lipase and cholesteryl ester transfer protein

Background. Genetic susceptibility contributes to the risk of diabetic neph ropathy. Lipid disorders may favour diabetic nephropathy. Thus polymorphism s 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 lip oprotein lipase (LPL), cholesteryl ester transfer protein (CETP) and apolip oprotein epsilon (Apo E) to the development of diabetic nephropathy by stud ying 494 type 1 diabetic patients with proliferative retinopathy and variou s stages of diabetic nephropathy (GENEDIAB Study). The selection process en sured that all patients had expressed their risk of chronic complications d ue to uncontrolled diabetes. Thus the nephropathy stages were largely influ enced by genetic background. The lipid profile included fasting plasma tota l cholesterol (TC), triglycerides (TG), apolipoprotein Al (Apo Al) and B (A po B), and lipoprotein (a) (Lp(a)). Genetic polymorphisms were determined b y PCR-based detection of Apo E (e2/e3/e4), LPL (mutation Asn 291 Ser) and C ETP (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 s tages 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 Al. However the genetic polymo rphism distributions of LPL, CETP and Apo <epsilon> did not differ in terms of renal complications. The study power to reject the null hypothesis was 58% for the Apo epsilon genotypes. Conclusion. These results support no or only marginal effects of a genetic basis for lipid disturbances encountered in diabetic nephropathy.