title: The PTPN22 620W allele confers susceptibility to systemic sclerosis: findings of a large case-control study of European Caucasians and a meta-analysis.
abstract: OBJECTIVE
  To determine whether genetic variants of the PTPN22 gene, including the R620W (1858C>T) missense single-nucleotide polymorphism (SNP), are associated with systemic sclerosis (SSc). Since PTPN22 is involved in multiple autoimmune diseases, we also examined the occurrence of a concomitant autoimmune disease. We then conducted a meta-analysis of the most recent studies of SSc in order to verify the association or lack of association between the PTPN22 1858C>T variant and SSc.
  
  
  METHODS
  Seven PTPN22 SNPs were analyzed in a French Caucasian cohort of 659 SSc patients and 504 healthy controls. All SSc patient sera were tested for the presence of autoantibodies against topoisomerase I (anti-topo I) and for anticentromere antibodies (ACAs).
  
  
  RESULTS
  The co-occurrence of an autoimmune disease was observed in 22% of the 416 SSc patients who were exhaustively screened. In 33 of the 416 patients (8%), the concomitant autoimmune disease was known to be associated with PTPN22 1858T; these patients were excluded prior to analysis. No association was detected for any of the SNPs tested. PTPN22 haplotype analysis identified a strong association between SSc and the presence of a risk haplotype carrying the 1858T allele (P = 1.52 x 10(-7)) and a protective haplotype carrying the 1858C allele (P = 2.20 x 10(-16)) in our French Caucasian population. The meta-analysis provided evidence that the PTPN22 1858T allele is involved in the genetic susceptibility to SSc in Caucasian (P = 8.39 x 10(-3), OR 1.08 [95% CI 1.02-1.15]) and mixed (P = 3.11 x 10(-3), OR 1.09 [95% CI 1.04-1.16]) populations, particularly in the anti-topo I-positive subset.
  
  
  CONCLUSIONS
  Our results indicate that PTPN22, a shared genetic factor of multiple autoimmune diseases, also contributes to the genetic background of SSc.
authors.affiliation: Université Paris 7, Paris, France. philippe.dieude@bch.aphp.fr
authors.forename: P
authors.initials: P
authors.lastname: Dieudé
authors.forename: M
authors.initials: M
authors.lastname: Guedj
authors.forename: J
authors.initials: J
authors.lastname: Wipff
authors.forename: J
authors.initials: J
authors.lastname: Avouac
authors.forename: E
authors.initials: E
authors.lastname: Hachulla
authors.forename: E
authors.initials: E
authors.lastname: Diot
authors.forename: B
authors.initials: B
authors.lastname: Granel
authors.forename: J
authors.initials: J
authors.lastname: Sibilia
authors.forename: J
authors.initials: J
authors.lastname: Cabane
authors.forename: O
authors.initials: O
authors.lastname: Meyer
authors.forename: L
authors.initials: L
authors.lastname: Mouthon
authors.forename: A
authors.initials: A
authors.lastname: Kahan
authors.forename: C
authors.initials: C
authors.lastname: Boileau
authors.forename: Y
authors.initials: Y
authors.lastname: Allanore
mesh_terms: D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D012595:Scleroderma, Systemic / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22