title: INPPL1 is associated with the metabolic syndrome in men with Type 1 diabetes, but not with diabetic nephropathy.
abstract: OBJECTIVE
  The metabolic syndrome is a frequent phenomenon in people with Type 1 diabetes and is associated with diabetic nephropathy. The aim of this study was to investigate if the INPPL1 (inositol polyphosphate phosphatase-like 1) gene encoding lipid phosphatase SHIP2 is associated with the metabolic syndrome and diabetic nephropathy in Finnish people with Type 1 diabetes.
  
  
  METHODS
  Participants were selected from the FinnDiane study for this cross-sectional study. The individuals were divided into controls without the metabolic syndrome (n = 1074) and cases with the metabolic syndrome (n = 1328), or into groups based upon their albumin excretion rate. Nine single-nucleotide polymorphisms covering the INPPL1 gene +/- 20 kb were genotyped. The associations between the single-nucleotide polymorphisms and outcome variables were analysed with the χ(2) test and logistic regression.
  
  
  RESULTS
  Two INPPL1 single-nucleotide polymorphisms, rs2276048 (silent mutation) and rs2276047 (intronic), were associated with the metabolic syndrome in men with odds ratios of 0.23 (95% CI 0.11-0.45, P = 2.1 × 10(-5) ), and 0.37 (0.21-0.65, P = 0.001), adjusted for age, duration of diabetes and history of smoking. When both sexes were included, these associations were less significant. No association between the genotyped single-nucleotide polymorphisms and diabetic nephropathy was observed.
  
  
  CONCLUSIONS
  INPPL1 gene variants may contribute to susceptibility to the metabolic syndrome in men with Type 1 diabetes, but not to diabetic nephropathy.
authors.affiliation: Department of Pathology, University of Helsinki, Helsinki, Finland.
authors.forename: M E
authors.initials: ME
authors.lastname: Hyvönen
authors.forename: P
authors.initials: P
authors.lastname: Ihalmo
authors.forename: C
authors.initials: C
authors.lastname: Forsblom
authors.forename: L
authors.initials: L
authors.lastname: Thorn
authors.forename: N
authors.initials: N
authors.lastname: Sandholm
authors.forename: S
authors.initials: S
authors.lastname: Lehtonen
authors.forename: P-H
authors.initials: PH
authors.lastname: Groop
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000453:epidemiology / Q000235:genetics*; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012737:Sex Factors; D012907:Smoking / Q000453:epidemiology
chemical_list: D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases