title: Common variant in the HMGA2 gene increases susceptibility to nephropathy in patients with type 2 diabetes.
abstract: OBJECTIVE
  Type 2 diabetes is a chronic metabolic disorder associated with devastating microvascular complications. Genome-wide association studies have identified more than 60 genetic variants associated with type 2 diabetes and/or glucose and insulin traits, but their role in the progression of diabetes is not established. The aim of this study was to explore whether these variants were also associated with the development of nephropathy in patients with type 2 diabetes.
  
  
  METHODS
  We studied 28 genetic variants in 2,229 patients with type 2 diabetes from the local Malmö Scania Diabetes Registry (SDR) published during 2007-2010. Diabetic nephropathy (DN) was defined as micro- or macroalbuminuria and/or end-stage renal disease. Estimated glomerular filtration rate (eGFR) was assessed using the MDRD-4 formula. Replication genotyping of rs1531343 was performed in diabetic (Steno type 2 diabetes [n = 345], Genetics of Diabetes Audit and Research in Tayside Scotland [Go-DARTS] [n = 784]) and non-diabetic (Malmö Preventive Project [n = 2,523], Botnia study [n = 2,247]) cohorts.
  
  
  RESULTS
  In the SDR, HMGA2 single-nucleotide polymorphism rs1531343 was associated with DN (OR 1.50, 95% CI 1.20, 1.87, p = 0.00035). In the combined analysis totalling 3,358 patients with type 2 diabetes (n = 1,233 cases, n = 2,125 controls), carriers of the C-allele had a 1.45-fold increased risk of developing nephropathy (95% CI 1.20, 1.75, p = 0.00010). Furthermore, the risk C-allele was associated with lower eGFR in patients with type 2 diabetes (n = 2,499, β ± SEM, -3.7 ± 1.2 ml/min, p = 0.002) and also in non-diabetic individuals (n = 17,602, β ± SEM, -0.008 ± 0.003 ml/min (log(                     e                   )), p = 0.006).
  
  
  CONCLUSIONS
  These data demonstrate that the HMGA2 variant seems to be associated with increased risk of developing nephropathy in patients with type 2 diabetes and lower eGFR in both diabetic and non-diabetic individuals and could thus be a common denominator in the pathogenesis of type 2 diabetes and kidney complications.
authors.affiliation: Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, CRC, Skåne University Hospital, Malmö, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Alkayyali
authors.forename: M
authors.initials: M
authors.lastname: Lajer
authors.forename: H
authors.initials: H
authors.lastname: Deshmukh
authors.forename: E
authors.initials: E
authors.lastname: Ahlqvist
authors.forename: H
authors.initials: H
authors.lastname: Colhoun
authors.forename: B
authors.initials: B
authors.lastname: Isomaa
authors.forename: P
authors.initials: P
authors.lastname: Rossing
authors.forename: L
authors.initials: L
authors.lastname: Groop
authors.forename: V
authors.initials: V
authors.lastname: Lyssenko
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D025743:HMGA2 Protein / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D025743:HMGA2 Protein