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A Single Nucleotide Polymorphism in Protein Tyrosine Phosphatase PTP-1B Is Associated with Protection from Diabetes or Impaired Glucose Tolerance in Oji-Cree

John P. Robarts Research Institute (A.M., H.C., R.A.H.), London, Ontario, Canada N6A 5K8; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto (B.Z., A.J.G.H.), Ontario, Canada M5G 1X5; Thames Valley Family Practice Research Unit, University of Western Ontario (S.B.H.), London, Ontario, Canada N6G 4X8; Department of Biochemistry and Molecular Biology, Merck Frosst Center for Therapeutic Research (B.P.K.), Pointe Claire-Dorval, Quebec, Canada H9R 4P8

Address all correspondence and requests for reprints to: Robert A. Hegele, M.D., Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, 406-100 Perth Drive, London, Ontario, Canada N6A 5K8. E-mail: robert.hegele{at}rri.on.ca

Abstract

Several lines of evidence support a role for protein tyrosine phosphatase 1B (PTP-1B) in metabolism, and specifically in insulin sensitivity and obesity. We report the development of reagents for the amplification and sequencing of the PTP-1B gene, which has resulted in the identification of a novel single nucleotide polymorphism (SNP), designated 981C T. We found a significant association between this SNP and the risk of either impaired glucose tolerance (IGT) or type 2 diabetes in the Oji-Cree of Sandy Lake, Ontario, Canada. Six hundred and fifty-three subjects were genotyped using PCR amplification of exon 8, followed by digestion with the restriction enzyme AvaI. Sixty-eight subjects were heterozygotes, and none was a homozygote. Thus, the overall frequencies of the C allele and the T allele were 0.948 and 0.052, respectively. Subjects with the PTP-1B 981T/981C genotype were approximately 40% less likely to have IGT or diabetes as subjects with the 981C/981C genotype (P = 0.040). There was no difference in quantitative traits among subjects grouped according to the PTP-1B 981CT SNP genotype. These very preliminary findings suggest that genomic variation in PTP-1B is associated with a reduced risk of diabetes and are consistent with the idea that this protein is important in metabolism.

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