title: Association analysis of the R620W polymorphism of protein tyrosine phosphatase PTPN22 in systemic lupus erythematosus families: increased T allele frequency in systemic lupus erythematosus patients with autoimmune thyroid disease.
abstract: OBJECTIVE
  Recent case-control studies show associations of the minor T allele (of the C1858T single-nucleotide polymorphism corresponding to the R620W amino acid substitution) of PTPN22 with multiple autoimmune diseases, including systemic lupus erythematosus (SLE). We performed family-based association studies of this polymorphism in 4 independent cohorts containing SLE patients and their parents and/or other family members.
  
  
  METHODS
  A total of 2,689 individuals from 902 independent Caucasian families with SLE were genotyped using polymerase chain reaction pyrosequencing (cohorts 1 and 2) and the Sequenom MassArray system (cohorts 3 and 4). The transmission disequilibrium test (TDT) and the pedigree disequilibrium test (PDT) were conducted to assess the evidence of association.
  
  
  RESULTS
  The 1858 C > T allele frequencies of the parents showed no deviation from Hardy-Weinberg equilibrium within each cohort. No evidence of preferential transmission of the T allele from heterozygous parents to their affected offspring was observed in each of the 4 cohorts or in the combined sample. Consistent with the TDT result, the PDT analysis revealed no significant association between the T allele and SLE. In 54 of the 661 SLE patients (cohorts 1 and 3) with documented autoimmune thyroid disease, the T allele frequency was higher than in individuals with SLE alone (16.7% versus 8.5%; P = 0.008, odds ratio 2.16 [95% confidence interval 1.25-3.72]).
  
  
  CONCLUSIONS
  The R620W polymorphism of the PTPN22 gene is not a major risk allele for SLE susceptibility in our sample of Caucasian individuals from northern America, the UK, or Finland, but it appears to be a risk factor for the concurrent autoimmune diseases of autoimmune thyroid disease and SLE.
authors.affiliation: David Geffen School of Medicine, University of California, Los Angeles, 90095, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.forename: Rita M
authors.initials: RM
authors.lastname: Cantor
authors.forename: Deborah S Cunninghame
authors.initials: DS
authors.lastname: Graham
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Lingren
authors.forename: Lisa
authors.initials: L
authors.lastname: Farwell
authors.forename: Philip L De
authors.initials: PL
authors.lastname: Jager
authors.forename: Nunzio
authors.initials: N
authors.lastname: Bottini
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Grossman
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wallace
authors.forename: Bevra H
authors.initials: BH
authors.lastname: Hahn
authors.forename: Heikki
authors.initials: H
authors.lastname: Julkunen
authors.forename: Lee A
authors.initials: LA
authors.lastname: Hebert
authors.forename: Brad H
authors.initials: BH
authors.lastname: Rovin
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Birmingham
authors.forename: John D
authors.initials: JD
authors.lastname: Rioux
authors.forename: C Yung
authors.initials: CY
authors.lastname: Yu
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Vyse
authors.forename: Betty P
authors.initials: BP
authors.lastname: Tsao
mesh_terms: D001120:Arginine; D001327:Autoimmune Diseases / Q000150:complications / Q000235:genetics*; D015331:Cohort Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000235:genetics*; D011110:Polymorphism, Genetic; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D013959:Thyroid Diseases / Q000150:complications / Q000235:genetics*; D014364:Tryptophan; D044465:White People / Q000235:genetics
chemical_list: D014364:Tryptophan; D001120:Arginine; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases