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.
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 RApatients 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.
Authors: Wan R Wan Taib; Deborah J Smyth; Marilyn E Merriman; Nicola Dalbeth; Peter J Gow; Andrew A Harrison; John Highton; Peter B B Jones; Lisa Stamp; Sophia Steer; John A Todd; Tony R Merriman Journal: PLoS One Date: 2010-10-21 Impact factor: 3.240
Authors: P Machado; I Castrejon; W Katchamart; R Koevoets; B Kuriya; M Schoels; L Silva-Fernández; K Thevissen; W Vercoutere; E Villeneuve; D Aletaha; L Carmona; R Landewé; D van der Heijde; J W J Bijlsma; V Bykerk; H Canhão; A I Catrina; P Durez; C J Edwards; M D Mjaavatten; B F Leeb; B Losada; E M Martín-Mola; P Martinez-Osuna; C Montecucco; U Müller-Ladner; M Østergaard; B Sheane; R M Xavier; J Zochling; C Bombardier Journal: Ann Rheum Dis Date: 2010-08-19 Impact factor: 19.103
Authors: Anne Barton; Wendy Thomson; Xiayi Ke; Steve Eyre; Anne Hinks; John Bowes; Laura Gibbons; Darren Plant; Anthony G Wilson; Ioanna Marinou; Ann Morgan; Paul Emery; Sophia Steer; Lynne Hocking; David M Reid; Paul Wordsworth; Pille Harrison; Jane Worthington Journal: Hum Mol Genet Date: 2008-04-22 Impact factor: 6.150