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.
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.
Wu
Hui
H
David Geffen School of Medicine, University of California, Los Angeles, 90095, USA.
Cantor
Rita M
RM
Graham
Deborah S Cunninghame
DS
Lingren
Cecilia M
CM
Farwell
Lisa
L
Jager
Philip L De
PL
Bottini
Nunzio
N
Grossman
Jennifer M
JM
Wallace
Daniel J
DJ
Hahn
Bevra H
BH
Julkunen
Heikki
H
Hebert
Lee A
LA
Rovin
Brad H
BH
Birmingham
Dan J
DJ
Rioux
John D
JD
Yu
C Yung
CY
Kere
Juha
J
Vyse
Timothy J
TJ
Tsao
Betty P
BP
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
D014364:Tryptophan; D001120:Arginine; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D017027:Protein Tyrosine Phosphatases