M Traurig1, R L Hanson, S Kobes, C Bogardus, L J Baier. 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.
Abstract
AIM/HYPOTHESIS: 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. RESULTS: 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. CONCLUSIONS/ INTERPRETATION: 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.
AIM/HYPOTHESIS: 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. RESULTS: 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. CONCLUSIONS/ INTERPRETATION: 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.
Authors: Nicola J Spencer-Jones; Xiaoling Wang; Harold Snieder; Tim D Spector; Nicholas D Carter; Sandra D O'Dell Journal: Diabetes Date: 2005-11 Impact factor: 9.461
Authors: Jennifer L Bento; Nicholette D Palmer; Josyf C Mychaleckyj; Leslie A Lange; Carl D Langefeld; Stephen S Rich; Barry I Freedman; Donald W Bowden Journal: Diabetes Date: 2004-11 Impact factor: 9.461
Authors: Nicholette D Palmer; Jennifer L Bento; Josyf C Mychaleckyj; Carl D Langefeld; Joel K Campbell; Jill M Norris; Stephen M Haffner; Richard N Bergman; Donald W Bowden Journal: Diabetes Date: 2004-11 Impact factor: 9.461
Authors: Jose C Florez; Christina M Agapakis; Noël P Burtt; Maria Sun; Peter Almgren; Lennart Råstam; Tiinamaija Tuomi; Daniel Gaudet; Thomas J Hudson; Mark J Daly; Kristin G Ardlie; Joel N Hirschhorn; Leif Groop; David Altshuler Journal: Diabetes Date: 2005-06 Impact factor: 9.461
Authors: Olavi Ukkola; Tuomo Rankinen; Timo Lakka; Arthur S Leon; James S Skinner; Jack H Wilmore; D C Rao; Y A Kesäniemi; Claude Bouchard Journal: Obes Res Date: 2005-05
Authors: S Lillioja; D M Mott; M Spraul; R Ferraro; J E Foley; E Ravussin; W C Knowler; P H Bennett; C Bogardus Journal: N Engl J Med Date: 1993-12-30 Impact factor: 91.245
Authors: S Ghosh; R M Watanabe; T T Valle; E R Hauser; V L Magnuson; C D Langefeld; D S Ally; K L Mohlke; K Silander; K Kohtamäki; P Chines; J Balow; G Birznieks; J Chang; W Eldridge; M R Erdos; Z E Karanjawala; J I Knapp; K Kudelko; C Martin; A Morales-Mena; A Musick; T Musick; C Pfahl; R Porter; J B Rayman Journal: Am J Hum Genet Date: 2000-10-13 Impact factor: 11.043
Authors: Joshua P Lewis; Nicholette D Palmer; Jennifer B Ellington; Jasmin Divers; Maggie C Y Ng; Lingyi Lu; Carl D Langefeld; Barry I Freedman; Donald W Bowden Journal: Genomics Date: 2010-07-30 Impact factor: 5.736
Authors: April J Stull; Zhong Q Wang; Xian H Zhang; Yongmei Yu; William D Johnson; William T Cefalu Journal: Diabetes Date: 2012-04-03 Impact factor: 9.461