title: A functional polymorphism (1858C/T) in the PTPN22 gene is linked and associated with type I diabetes in multiplex families.
abstract: Type I diabetes (T1D) is a complex disorder, which arises from the autoimmune destruction of the insulin-secreting beta cells of the pancreas leading to a life-long dependence on exogenous insulin. A recent study of T1D cases and controls provided evidence for association between an allele of a functional single-nucleotide polymorphism (SNP) in the PTPN22 gene and T1D. In the current study, this SNP was genotyped in a collection of 406 multiplex T1D families. Significant evidence of the combined presence of association and linkage to T1D was obtained (P = 2.5 x 10(-5)). Linkage studies in subsets of families defined by PTPN22 SNP genotypes suggest possible interaction with loci on chromosomes 3 and 21. Previous genome scans in this collection of T1D families, and others, have not yielded significant evidence of linkage in the region of the PTPN22 locus. However, the highly significant evidence of allelic association suggests that variation at, or near, this functional SNP contributes to the risk of T1D.
authors.affiliation: Molecular Genetics Program, Benaroya Research Institute, 1201 Ninth Ave, Seattle, WA 98101, USA.
authors.forename: S
authors.initials: S
authors.lastname: Onengut-Gumuscu
authors.forename: K G
authors.initials: KG
authors.lastname: Ewens
authors.forename: R S
authors.initials: RS
authors.lastname: Spielman
authors.forename: P
authors.initials: P
authors.lastname: Concannon
mesh_terms: D000483:Alleles; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D012307:Risk Factors
chemical_list: C516765:PTPN22 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases