INPPL1 is associated with the metabolic syndrome in men with Type 1 diabetes, but not with diabetic nephropathy

• Published in: Diabetic medicine 2012-12, Vol.29 (12), p.1589-1595
• Main Authors: Hyvönen, M. E., Ihalmo, P., Forsblom, C., Thorn, L., Sandholm, N., Lehtonen, S., Groop, P.-H.
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Cohort Studies; Cross-Sectional Studies; Diabetes; Diabetes Mellitus, Type 1 - epidemiology; Diabetes Mellitus, Type 1 - genetics; Diabetes. Impaired glucose tolerance; Diabetic Nephropathies - epidemiology; Diabetic Nephropathies - genetics; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Feeding. Feeding behavior; Female; Finland - epidemiology; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; Genotype; Humans; Kidneys; Male; Medical sciences; Metabolic syndrome; Metabolic Syndrome - epidemiology; Metabolic Syndrome - genetics; Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; Phosphoric Monoester Hydrolases - genetics; Polymorphism; Polymorphism, Single Nucleotide - genetics; Sex Factors; Smoking - epidemiology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1111/j.1464-5491.2012.03668.x

Diabet. Med. 29, 1589–1595 (2012) Aims  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 χ2 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.