title: Evaluating the role of the 620W allele of protein tyrosine phosphatase PTPN22 in Crohn's disease and multiple sclerosis.
abstract: The 620W allele of PTPN22 has been associated with susceptibility to several different forms of chronic inflammatory disease, including Type 1 diabetes (T1D), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and autoimmune thyroiditis (AIT). We set out to explore its possible role in two other inflammatory diseases: multiple sclerosis (MS) and Crohn's disease (CD). In our cohort of 496 MS trios from the United Kingdom, we observed reduced transmission of the PTPN22 620W allele. The CD sample consisted of 169 trios as well as 249 cases of CD with their 207 matched control subjects collected in the province of Québec, Canada; there was also no evidence of association between the PTPN22 620W allele and susceptibility for CD. Pooled analyses combining our data with published data assessed a total of 1496 cases of MS and 1019 cases of CD but demonstrated no evidence of association with either disease. Given the modest odds ratios of known risk alleles for inflammatory diseases, these analyses do not exclude a role for the PTPN22 allele in susceptibility to CD or MS, but they do suggest that such a putative role would probably be more modest than that reported so far in T1D, RA, SLE, and AIT.
authors.affiliation: Center for Neurologic Diseases, Department of Neurology, Brigham & Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA. pdejager@rics.bwh.harvard.edu
authors.forename: Philip L
authors.initials: PL
authors.lastname: De Jager
authors.forename: Stephen
authors.initials: S
authors.lastname: Sawcer
authors.forename: Alicja
authors.initials: A
authors.lastname: Waliszewska
authors.forename: Lisa
authors.initials: L
authors.lastname: Farwell
authors.forename: Gary
authors.initials: G
authors.lastname: Wild
authors.forename: Albert
authors.initials: A
authors.lastname: Cohen
authors.forename: Diane
authors.initials: D
authors.lastname: Langelier
authors.forename: Alain
authors.initials: A
authors.lastname: Bitton
authors.forename: Alastair
authors.initials: A
authors.lastname: Compston
authors.forename: David A
authors.initials: DA
authors.lastname: Hafler
authors.forename: John D
authors.initials: JD
authors.lastname: Rioux
mesh_terms: D000483:Alleles; D002170:Canada; D016022:Case-Control Studies; D003424:Crohn Disease / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007249:Inflammation; D015233:Models, Statistical; D009103:Multiple Sclerosis / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D012306:Risk; D006113:United Kingdom
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