Polymorphisms in Type-II SH2 domain-containing Inositol 5-Phosphatase (INPPL1, SHIP2) are Associated with Physiological Abnormalities of the Metabolic Syndrome
[en] 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
Polymorphisms in Type-II SH2 domain-containing Inositol 5-Phosphatase (INPPL1, SHIP2) are Associated with Physiological Abnormalities of the Metabolic Syndrome
Publication date :
2004
Journal title :
Diabetes
ISSN :
0012-1797
eISSN :
1939-327X
Publisher :
American Diabetes Association, Alexandria, United States - Virginia
Volume :
53
Pages :
1900-1904
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
The Wellcome Trust (057733), the Wellcome Cardiovascular Functional Genomics Initiative (066780/Z/01/Z), and Diabetes U.K. (RD96/0001270)
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