title: 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. Genétique de la Nephropathie Diabétique Study Group. Données Epidémiologiques sur le Syndrome d'Insulino-Résistance Study Group.
abstract: 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 epsilon (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 epsilon (e2/e3/e4), LPL (mutation Asn 291 Ser) and CETP (TAQ:IB 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 epsilon did not differ in terms of renal complications. The study power to reject the null hypothesis was 58% for the Apo epsilon genotypes.
  
  
  CONCLUSIONS
  These results support no or only marginal effects of a genetic basis for lipid disturbances encountered in diabetic nephropathy.
authors.affiliation: Médecine B, University Hospital, Angers, France.
authors.forename: S
authors.initials: S
authors.lastname: Hadjadj
authors.forename: Y
authors.initials: Y
authors.lastname: Gallois
authors.forename: G
authors.initials: G
authors.lastname: Simard
authors.forename: B
authors.initials: B
authors.lastname: Bouhanick
authors.forename: P
authors.initials: P
authors.lastname: Passa
authors.forename: A
authors.initials: A
authors.lastname: Grimaldi
authors.forename: P
authors.initials: P
authors.lastname: Drouin
authors.forename: J
authors.initials: J
authors.lastname: Tichet
authors.forename: M
authors.initials: M
authors.lastname: Marre
mesh_terms: D000328:Adult; D001057:Apolipoproteins E / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D053480:Cholesterol Ester Transfer Proteins; D002908:Chronic Disease; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1; D003928:Diabetic Nephropathies / Q000097:blood / Q000235:genetics*; D005260:Female; D005838:Genotype; D006023:Glycoproteins; D006801:Humans; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D001057:Apolipoproteins E; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D008055:Lipids; D008071:Lipoprotein Lipase