title: Association testing of the protein tyrosine phosphatase 1B gene (PTPN1) with type 2 diabetes in 7,883 people.
abstract: Protein tyrosine phosphatase (PTP)-1B, encoded by the PTPN1 gene, inactivates the insulin signal transduction cascade by dephosphorylating phosphotyrosine residues in insulin signaling molecules. Due to its chromosomal location under a chromosome 20 linkage peak and the metabolic effects of its absence in knockout mice, it is a candidate gene for type 2 diabetes. Recent studies have associated common sequence variants in PTPN1 with type 2 diabetes and diabetes-related phenotypes. We sought to replicate the association of common single nucleotide polymorphisms (SNPs) and haplotypes in PTPN1 with type 2 diabetes, fasting plasma glucose, and insulin sensitivity in a large collection of subjects. We assessed linkage disequilibrium, selected tag SNPs, and typed these markers in 3,347 cases of type 2 diabetes and 3,347 control subjects as well as 1,189 siblings discordant for type 2 diabetes. Despite power estimated at >95% to replicate the previously reported associations, no statistically significant evidence of association was observed between PTPN1 SNPs or common haplotypes with type 2 diabetes or with diabetic phenotypes.
authors.affiliation: Department of Endocrinology, University Hospital MAS, Lund University, Malmö, Sweden.
authors.forename: Jose C
authors.initials: JC
authors.lastname: Florez
authors.forename: Christina M
authors.initials: CM
authors.lastname: Agapakis
authors.forename: Noël P
authors.initials: NP
authors.lastname: Burtt
authors.forename: Maria
authors.initials: M
authors.lastname: Sun
authors.forename: Peter
authors.initials: P
authors.lastname: Almgren
authors.forename: Lennart
authors.initials: L
authors.lastname: Råstam
authors.forename: Tiinamaija
authors.initials: T
authors.lastname: Tuomi
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaudet
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hudson
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Daly
authors.forename: Kristin G
authors.initials: KG
authors.lastname: Ardlie
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.forename: David
authors.initials: D
authors.lastname: Altshuler
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D002874:Chromosome Mapping; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; 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