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Diabetes 53:1900-1904, 2004
© 2004 by the American Diabetes Association, Inc.

Brief Genetics Report

Polymorphisms in Type II SH2 Domain–Containing Inositol 5-Phosphatase (INPPL1, SHIP2) Are Associated With Physiological Abnormalities of the Metabolic Syndrome

Pamela J. Kaisaki1, Marc Delépine2, Peng Y. Woon1, Liam Sebag-Montefiore1, Steven P. Wilder1, Stephan Menzel1, Nathalie Vionnet2, Evelyne Marion3, Jean-Pierre Riveline4, Guillaume Charpentier4, Stéphane Schurmans3, Jonathan C. Levy5, Mark Lathrop2, Martin Farrall6, and Dominique Gauguier1

1 The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K
2 National Centre for Genotyping, Evry, France
3 Institut de Recherches en Biologie Humaine et Moléculaire, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, Gosselies, Belgium
4 Service d’Endocrinologie-Diabétologie, CH Sud Francilien, Corbeil-Essonnes, France
5 Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, U.K
6 Department of Cardiovascular Medicine, University of Oxford, Oxford, U.K

Type II SH2 domain–containing inositol 5-phosphatase (INPPL1, or SHIP2) plays an important role in the control of insulin sensitivity. INPPL1 mutations affecting gene function have been found in rat models of type 2 diabetes and hypertension and in type 2 diabetic patients. We investigated the influence of nucleotide variation in INPPL1 on components of the metabolic syndrome. Following comprehensive resequencing of the gene, we genotyped 12 informative polymorphisms in 1,304 individuals from 424 British type 2 diabetes families that were characterized for several metabolic phenotypes. We have found highly significant associations of single nucleotide polymorphisms (SNPs) and haplotypes of INPPL1 with hypertension as well as with other components of the metabolic syndrome. In a cohort of 905 French type 2 diabetic patients, we found evidence of association of INPPL1 SNPs with the presence of hypertension. We conclude that INPPL1 variants may impact susceptibility to disease and/or to subphenotypes involved in the metabolic syndrome in some diabetic patients.

Address correspondencereprint requests to Pamela J. Kaisaki, The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Headington, Oxford OX3 7BN, U.K. E-mail: pamela.kaisaki{at}well.ox.ac.uk

Abbreviations: DIF, Diabetes in Families; PDT, pedigree disequilibrium test; SNP, single nucleotide polymorphism


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Copyright © 2004 by the American Diabetes Association.