title: Role of alpha-adducin DNA polymorphisms in the genetic predisposition to diabetic nephropathy.
abstract: BACKGROUND
  There is substantial evidence for genetic susceptibility to diabetic nephropathy. In particular, genes that predispose to hypertension in the general population may confer susceptibility to nephropathy in patients with diabetes. A Gly460Trp variant in the alpha-adducin gene has been associated with essential hypertension. Our aim was to screen the alpha-adducin gene for polymorphisms and to determine if any variants predisposed patients with diabetes to nephropathy. A secondary objective was to assess for association between the Gly460Trp variant and hypertension.
  
  
  METHODS
  The exons of the alpha-adducin gene were resequenced in 30 individuals. Selected variants were then genotyped in 155 patients with type 1 diabetes and nephropathy (cases) and 216 persons with type 1 diabetes but no evidence of nephropathy (controls) from Northern Ireland and in 95 cases and 118 controls from the Irish Republic.
  
  
  RESULTS
  Eleven polymorphisms were detected, of which six were novel and three caused amino-acid substitutions. The Gly460Trp and a novel Ser617Cys polymorphism were in strong linkage disequilibrium (D' = 0.98). Neither the genotype nor allele frequencies for the Gly460Trp polymorphism (P = 0.89 and 0.93 respectively) or the Ser617Cys polymorphism (P = 0.46 and 0.76) were significantly different between cases and controls when the Northern Ireland and Irish Republic sample groups were combined. Carriage of the 460Trp allele was not significantly associated with systolic or diastolic blood pressure in either the cases (P = 0.48 and 0.06, respectively) or in the controls (P = 0.50 and 0.94, respectively).
  
  
  CONCLUSIONS
  Variation in the alpha-adducin gene does not play a major role in the development of nephropathy in persons with type 1 diabetes in the Irish population. Furthermore, the Gly460Trp variant was not associated with hypertension in this population.
authors.affiliation: Nephrology Research Group, Queen's University of Belfast, Northern Ireland. BryanConway@ntlworld.com
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Conway
authors.forename: Rosalind
authors.initials: R
authors.lastname: Martin
authors.forename: Amy-Jayne
authors.initials: AJ
authors.lastname: McKnight
authors.forename: David A
authors.initials: DA
authors.lastname: Savage
authors.forename: Hugh R
authors.initials: HR
authors.lastname: Brady
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Maxwell
mesh_terms: D000328:Adult; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005091:Exons / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000502:physiology; D005838:Genotype; D005998:Glycine / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000235:genetics; D015810:Linkage Disequilibrium; D009660:Northern Ireland / Q000453:epidemiology; D011110:Polymorphism, Genetic / Q000235:genetics*; D016036:Seroepidemiologic Studies; D014357:Trypsin / Q000235:genetics; D000099291:Adducins
chemical_list: D002148:Calmodulin-Binding Proteins; D003598:Cytoskeletal Proteins; D005998:Glycine; D014357:Trypsin; D000099291:Adducins