title: ABCG8 polymorphisms and renal disease in type 2 diabetic patients.
abstract: OBJECTIVE
  Sterols, bile acids and their receptors have been involved in diabetic nephropathy. The ATP-binding cassette transporters G5 and G8 (ABCG5 and ABCG8) play an important role in intestinal sterol absorption and bile acid secretion. The aim of our study was to assess the associations between two ABCG8 coding polymorphisms, T400K and D19H, and the incidence of renal events in type 2 diabetic subjects.
  
  
  METHODS
  Participants were the 3137 French type 2 diabetic subjects with micro- or macro-albuminuria from the genetic substudy of the DIABHYCAR trial. The mean duration of follow-up was 4years. Renal events were defined as a doubling of serum creatinine concentration or end-stage renal disease at follow-up. We then used a second population (DIAB2NEPHROGENE) of 2140 type 2 diabetic patients for the purpose of validation.
  
  
  RESULTS
  In DIABHYCAR, the 400K allele was significantly associated with a higher risk of incident renal events in a multiple adjusted model (HR: 1.75 [95% CI 1.20-2.56], P=0.003). This association was still significant after further adjustments for baseline values of estimated glomerular filtration rate and urinary albumin excretion. In the validation population, the 400K allele was associated with the prevalence of end-stage renal disease (OR=2.01 [95% CI 1.15-3.54], P=0.015). No significant association was found between the D19H polymorphism and the risk of diabetic nephropathy.
  
  
  CONCLUSIONS
  A polymorphism of the sterol transporter ABCG8 has been associated with the prevalence of end-stage renal disease and with the incidence of new renal events in type 2 diabetic patients.
authors: INSERM, Centre de Recherche des Cordeliers, Research Unit 1138, Paris, France; Univ Pierre et Marie Curie, Paris, France.
authors: Anthony
authors: A
authors: Nicolas
authors: INSERM, Centre de Recherche des Cordeliers, Research Unit 1138, Paris, France.
authors: Sehrish
authors: S
authors: Fatima
authors: INSERM, Centre de Recherche des Cordeliers, Research Unit 1138, Paris, France; Univ Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors: Amel
authors: A
authors: Lamri
authors: INSERM, Centre de Recherche des Cordeliers, Research Unit 1138, Paris, France.
authors: Naima
authors: N
authors: Bellili-Muñoz
authors: University Hospital of Tours, Diabetology and Nephrology Department, Tours, France.
authors: Jean-Michel
authors: JM
authors: Halimi
authors: Université de Poitiers, UFR Médecine Pharmacie, CIC1402, Poitiers, France; CHU de Poitiers, Service Endocrinologie, Diabétologie, Pole DUNE & Centre d'investigation Clinique, Poitiers, France; INSERM, CIC1402, Poitiers, France.
authors: Pierre-Jean
authors: PJ
authors: Saulnier
authors: Université de Poitiers, UFR Médecine Pharmacie, CIC1402, Poitiers, France; CHU de Poitiers, Service Endocrinologie, Diabétologie, Pole DUNE & Centre d'investigation Clinique, Poitiers, France; INSERM, CIC1402, Poitiers, France.
authors: Samy
authors: S
authors: Hadjadj
authors: INSERM, Centre de Recherche des Cordeliers, Research Unit 1138, Paris, France.
authors: Gilberto
authors: G
authors: Velho
authors: INSERM, Centre de Recherche des Cordeliers, Research Unit 1138, Paris, France; Univ Paris Diderot, Sorbonne Paris Cité, Paris, France; Assistance Publique Hôpitaux de Paris, Bichat Hospital, Department of Diabetology, Endocrinology and Nutrition, Paris, France.
authors: Michel
authors: M
authors: Marre
authors: INSERM, Centre de Recherche des Cordeliers, Research Unit 1138, Paris, France; Univ Paris Diderot, Sorbonne Paris Cité, Paris, France; Assistance Publique Hôpitaux de Paris, Bichat Hospital, Department of Diabetology, Endocrinology and Nutrition, Paris, France.
authors: Ronan
authors: R
authors: Roussel
authors: INSERM, Centre de Recherche des Cordeliers, Research Unit 1138, Paris, France; Univ Paris Diderot, Sorbonne Paris Cité, Paris, France. Electronic address: frederic.fumeron@inserm.fr.
authors: Frédéric
authors: F
authors: Fumeron
mesh_terms: D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000368:Aged; D000419:Albuminuria / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D005919:Glomerular Filtration Rate; D006801:Humans; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000235:genetics; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D015995:Prevalence; D016896:Treatment Outcome
chemical_list: C416946:ABCG8 protein, human; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters
keywords: ABCG8 transporter; Association study; Diabetic nephropathy; End-stage renal disease; Genetic polymorphisms