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
| Autor: | Philip L. De Jager, John D. Rioux, Daniel J. Wallace, Cecilia M. Lingren, Heikki Julkunen, Brad H. Rovin, C. Yung Yu, Jennifer M. Grossman, Daniel J. Birmingham, Bevra H. Hahn, Juha Kere, Timothy J. Vyse, Lee A. Hebert, Betty P. Tsao, Nunzio Bottini, Hui Wu, Rita M. Cantor, Lisa Farwell, Deborah S. Cunninghame Graham |
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| Rok vydání: | 2005 |
| Předmět: |
Immunology
Arginine White People Autoimmune Diseases Cohort Studies PTPN22 03 medical and health sciences 0302 clinical medicine Gene Frequency Rheumatology immune system diseases medicine Humans Lupus Erythematosus Systemic Immunology and Allergy Genetic Predisposition to Disease Pharmacology (medical) Allele skin and connective tissue diseases Allele frequency 030304 developmental biology Genetic association 030203 arthritis & rheumatology Autoimmune disease 0303 health sciences Polymorphism Genetic Lupus erythematosus business.industry Tryptophan Protein Tyrosine Phosphatase Non-Receptor Type 22 Transmission disequilibrium test medicine.disease Thyroid Diseases Connective tissue disease 3. Good health Protein Tyrosine Phosphatases business |
| Zdroj: | Arthritis & Rheumatism. 52:2396-2402 |
| ISSN: | 1529-0131 0004-3591 |
| DOI: | 10.1002/art.21223 |
| Popis: | 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]). Conclusion 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. |
| Databáze: | OpenAIRE |
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