title: Mutation screening of PTPN22: association of the 1858T-allele with Addison's disease.
abstract: The tyrosine-protein phosphatase non-receptor type 22 (PTPN22) gene was recently identified as an important genetic susceptibility factor in several autoimmune diseases. The increased risk has been broadly explained by the 1858T-allele (rs2476601). As two smaller studies on Addison's disease (AD) have shown diverging results, we aimed to elucidate the predisposing effect of the single-nucleotide polymorphism (SNP) 1858CT in a larger population of AD patients, especially focusing on the AD patients with known autoimmune etiology. We also screened for unknown rare or common variants in the PTPN22 gene that could predispose for AD. The case-control study of Norwegian AD patients (n=332) and controls (n=990) showed a significant association between autoimmune AD (n=302) and the PTPN22 1858T risk allele (P=0.016). The association of AD with 1858T was supported by a meta-analysis combining our genotype data with that of others published previously (P=0.003). The mutation screening of PTPN22 in AD patients (n=332) and controls (n=112) revealed eight missense variants, five of which have not been reported previously. In conclusion, the 1858T-allele is a PTPN22 genetic susceptibility factor for autoimmune AD. Other rare variants in PTPN22 do occur, and may also be involved in the pathogenesis.
authors.affiliation: Institute of Medical Genetics, University of Oslo, Department of Medical Genetics, Ullevaal University Hospital, Oslo, Norway. beate.skinningsrud@medisin.uio.no
authors.forename: Beate
authors.initials: B
authors.lastname: Skinningsrud
authors.forename: Eystein S
authors.initials: ES
authors.lastname: Husebye
authors.forename: Kristina
authors.initials: K
authors.lastname: Gervin
authors.forename: Kristian
authors.initials: K
authors.lastname: Løvås
authors.forename: Anne
authors.initials: A
authors.lastname: Blomhoff
authors.forename: Anette B
authors.initials: AB
authors.lastname: Wolff
authors.forename: E Helen
authors.initials: EH
authors.lastname: Kemp
authors.forename: Thore
authors.initials: T
authors.lastname: Egeland
authors.forename: Dag E
authors.initials: DE
authors.lastname: Undlien
mesh_terms: D000224:Addison Disease / Q000453:epidemiology / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D009664:Norway / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D006113:United Kingdom / Q000453:epidemiology
chemical_list: C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22