Protein tyrosine phosphatase 1B is not a major susceptibility gene for type 2 diabetes mellitus or obesity among Pima Indians
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.
Materials and methods
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.
- Ghosh S, Watanabe RM, Valle TT et al (2000) The Finland–United States investigation of non-insulin-dependent diabetes mellitus genetics (FUSION) study. I. An autosomal genome scan for genes that predispose to type 2 diabetes. Am J Hum Genet 67:1174–1185
- Bento JL, Palmer ND, Mychaleckyj JC et al (2004) Association of protein tyrosine phosphatase 1B gene polymorphisms with type 2 diabetes. Diabetes 53:3007–3012 CrossRef
- Palmer ND, Bento JL, Mychaleckyj JC et al (2004) Association of protein tyrosine phosphatase 1B gene polymorphisms with measures of glucose homeostasis in Hispanic Americans: the insulin resistance atherosclerosis study (IRAS) family study. Diabetes 53:3013–3019 CrossRef
- Florez JC, Agapakis CM, Burtt NP et al (2005) Association testing of the protein tyrosine phosphatase 1B gene (PTPN1) with type 2 diabetes in 7,883 people. Diabetes 54:1884–1891 CrossRef
- Spencer-Jones NJ, Wang X, Snieder H, Spector TD, Carter ND, O’Dell SD (2005) Protein tyrosine phosphatase-1b gene PTPN1: selection of tagging single nucleotide polymorphisms and association with body fat, insulin sensitivity, and the metabolic syndrome in a normal female population. Diabetes 54:3296–3304 CrossRef
- Cheyssac C, Lecoeur C, Dechaume A et al (2006) Analysis of common PTPN1 gene variants in type 2 diabetes, obesity and associated phenotypes in the French population. BMC Med Genet 7:44 CrossRef
- Knowler WC, Pettitt DJ, Saad MF, Bennett PH (1990) Diabetes mellitus in the Pima Indians: incidence, risk factors and pathogenesis. Diabetes Metab Rev 6:1–27 CrossRef
- Vozarova de Courten B, Hanson RL, Funahashi T et al (2005) Common polymorphisms in the adiponectin gene ACDC are not associated with diabetes in Pima Indians. Diabetes 54:284–289 CrossRef
- Lillioja S, Mott DM, Spraul M et al (1993) Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of Pima Indians. N Engl J Med 329:1988–1992 CrossRef
- Hanson RL, Looker HC, Ma L, Muller YL, Baier LJ, Knowler WC (2006) Design and analysis of genetic association studies to finely map a locus identified by linkage analysis: sample size and power calculations. Ann Hum Genet 70:332–349 CrossRef
- Ukkola O, Rankinen T, Lakka T et al (2005) Protein tyrosine phosphatase 1B variant associated with fat distribution and insulin metabolism. Obes Res 13:829–834 CrossRef
- Echwald SM, Bach H, Vestergaard H et al (2002) A P387L variant in protein tyrosine phosphatase-1B (PTP-1B) is associated with type 2 diabetes and impaired serine phosphorylation of PTP-1B in vitro. Diabetes 51:1–6 CrossRef
- Protein tyrosine phosphatase 1B is not a major susceptibility gene for type 2 diabetes mellitus or obesity among Pima Indians
Volume 50, Issue 5 , pp 985-989
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Insulin sensitivity
- Pima Indians
- Type 2 diabetes
- Industry Sectors
- Author Affiliations
- 1. 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
- 2. National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, 445 North 5th Street, Phoenix, AZ, 85004, USA