title: A single nucleotide polymorphism in protein tyrosine phosphatase PTP-1B is associated with protection from diabetes or impaired glucose tolerance in Oji-Cree.
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 981C-->T 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.
authors.affiliation: John P. Robarts Research Institute, London, Ontario, Canada N6A 5K8.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mok
authors.forename: Henian
authors.initials: H
authors.lastname: Cao
authors.forename: Bernard
authors.initials: B
authors.lastname: Zinman
authors.forename: Anthony J G
authors.initials: AJ
authors.lastname: Hanley
authors.forename: Stewart B
authors.initials: SB
authors.lastname: Harris
authors.forename: Brian P
authors.initials: BP
authors.lastname: Kennedy
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
mesh_terms: D000328:Adult; D000483:Alleles; D003920:Diabetes Mellitus / Q000517:prevention & control*; D005260:Female; D005838:Genotype; D018149:Glucose Intolerance / Q000517:prevention & control*; D006579:Heterozygote; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000502:physiology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*
chemical_list: C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases