The 620W allele is the PTPN22 genetic variant conferring susceptibility to RA in a Dutch population

• Published in: Rheumatology (Oxford, England) Vol. 46; no. 4; pp. 617 - 621
• Main Authors: Wesoly, J., Hu, X., Thabet, M. M., Chang, M., Uh, H., Allaart, C. F., Toes, R. E. M., Houwing-Duistermaat, J. J., Begovich, A. B., Huizinga, T. W. J.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.04.2007; Oxford Publishing Limited (England)
• Subjects: Adult; Aged; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Biological and medical sciences; Diseases of the osteoarticular system; Gene Frequency; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Inflammatory joint diseases; Medical sciences; Middle Aged; Polymorphism, Single Nucleotide; Protein Tyrosine Phosphatase, Non-Receptor Type 22; Protein Tyrosine Phosphatases - genetics; Rheumatoid Factor - blood; Association study; PTPN22; Haplotype; RA; Immunopathology; Allele; Chronic; Rheumatoid arthritis; Diseases of the osteoarticular system; Autoimmune disease; Inflammatory joint disease; Genetic determinism
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/kel381

Objectives. A missense SNP, C1858T, in PTPN22 has been identified as a genetic risk factor for rheumatoid arthritis (RA). Subsequent work has suggested that other variants in this gene, in particular a haplotype marked by the minor allele of rs3789604, are associated with RA in white North Americans independent of C1858T. We tested this hypothesis in an independent white Dutch study. Methods. A total of 667 RA patients and 286 controls were genotyped for 13 PTPN22 single nucleotide polymorphisms (SNPs) by allele-specific kinetic polymerase chain reaction. rs3789604 was genotyped in an additional 410 RA and 270 UA patients participating in the Leiden early arthritis inception cohort. We conducted single-marker and haplotype association tests. Results. The sole haplotype strongly associated with RA in our Dutch population carries the PTPN22 1858T allele. A second haplotype identical at all other SNPs tested except 1858 was not associated with disease. No significant association of the haplotype tagged by the 3′ PTPN22 SNP, rs3789604, with RA susceptibility (P = 0.134) was observed in our sample set. Conclusion. We conclude that C1858T is the sole PTPN22 variant predisposing to RA in our white Dutch sample set.