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
Article first published online: 28 JUL 2005
Copyright © 2005 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 52, Issue 8, pages 2396–2402, August 2005
How to Cite
Wu, H., Cantor, R. M., Graham, D. S. C., Lingren, C. M., Farwell, L., Jager, P. L. D., Bottini, N., Grossman, J. M., Wallace, D. J., Hahn, B. H., Julkunen, H., Hebert, L. A., Rovin, B. H., Birmingham, D. J., Rioux, J. D., Yu, C. Y., Kere, J., Vyse, T. J. and Tsao, B. P. (2005), 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. Arthritis & Rheumatism, 52: 2396–2402. doi: 10.1002/art.21223
- Issue published online: 28 JUL 2005
- Article first published online: 28 JUL 2005
- Manuscript Accepted: 11 MAY 2005
- Manuscript Received: 14 DEC 2004
- NIH. Grant Number: R01-AR-43814
- National Institute of Arthritis and Musculoskeletal and Skin Diseases. Grant Number: P01-55546
- National Institute of Diabetes and Digestive and Kidney Diseases
- Arthritis National Research Foundation. Grant Number: 441347-UW-79871
- Paxson Family Foundation, and the Wellcome Trust
- Southern California Chapter of the Arthritis Foundation
- NIH. Grant Number: K08-NS-046341-02
- National Institute of Neurological Disorders and Stroke
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.
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.
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]).
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.