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

• Published in: Diabetologia 2007-05, Vol.50 (5), p.985-989
• Main Authors: Traurig, M, Hanson, R. L, Kobes, S, Bogardus, C, Baier, L. J
• Format: Article
• Language: English
• Subjects: Adult; Arizona - epidemiology; Biological and medical sciences; Diabetes; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Genetic Predisposition to Disease; Genotyping; Glucose; Haplotypes; Humans; Indians, North American - statistics & numerical data; Insulin; insulin resistance; Kidney diseases; Male; Medical sciences; Metabolic diseases; Middle Aged; noninsulin-dependent diabetes mellitus; Obesity; Obesity - epidemiology; Obesity - genetics; Phosphatase; Pima Indians; Polymorphism, Single Nucleotide; Protein Tyrosine Phosphatases - genetics; Proteins; PTPN1; Reference Values; SNPs; Statistical analysis
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-007-0611-6

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.