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Diabetologia. 2007 May;50(5):985-9. Epub 2007 Feb 27.

Protein tyrosine phosphatase 1B is not a major susceptibility gene for type 2 diabetes mellitus or obesity among Pima Indians.

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Diabetes Molecular Genetics Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, USA.



Single-nucleotide polymorphisms (SNPs) in the protein tyrosine phosphatase 1B gene (PTPN1) have been reported to be associated with type 2 diabetes in white subjects, and insulin sensitivity and fasting glucose levels in Hispanic Americans. In this study, we determined whether SNPs in PTPN1 also have a role in type 2 diabetes susceptibility in Pima Indians, a population with the world's highest reported prevalence and incidence rates of this disease.


Thirty-one SNPs across a 161-kb region encompassing PTPN1 were genotyped in 1,037 Pima Indians for association studies with type 2 diabetes and obesity.


Twenty-five of the SNPs had allele frequencies >0.05, and these SNPs fell into two linkage disequilibrium blocks (D' > 0.9). Block 1 contains six SNPs that span a 61-kb region upstream of PTPN1, while block 2 contains 19 SNPs that cover the entire PTPN1 gene. None of the SNPs, analysed individually or as haplotypes, was associated with either type 2 diabetes or obesity. However, three SNPs located in block 1 were nominally associated (p values ranging from 0.01 to 0.05) with insulin sensitivity as measured by the hyperinsulinaemic-euglycaemic clamp technique.


Based on our association results, we conclude that SNPs within PTPN1 are unlikely to have a major role in the aetiology of type 2 diabetes or obesity in Pima Indians.

[Indexed for MEDLINE]

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