%0 Journal Article %A Maria Seddighzadeh %A Antonio Gonzalez %A Bo Ding %A Aida Ferreiro-Iglesias %A Juan J. Gomez-Reino %A Rheumatoid Arthritis Network and Coordinated Project %A Lars Klareskog %A Lars Alfredsson %A Kyri Dunussi-Joannopoulos %A James D. Clark %A Leonid Padyukov %T Variants Within STAT Genes Reveal Association with Anticitrullinated Protein Antibody-negative Rheumatoid Arthritis in 2 European Populations %D 2012 %R 10.3899/jrheum.111284 %J The Journal of Rheumatology %P jrheum.111284 %X Objective STAT3 and 4 are, among other factors, critical for the interleukin 12 (IL-12)-mediated Th1 response, for transfer of IL-23 signals, and for survival and expansion of Th17 cells. We investigated the association of STAT3 and STAT4 polymorphisms with serologically distinct subgroups of rheumatoid arthritis (RA). Methods A total of 41 single-nucleotide polymorphisms (SNP) within STAT3 and STAT1-STAT4 loci were investigated in a Swedish cohort of 2043 RA cases and 1115 controls. Nine of the associated SNP were tested in a Spanish cohort of 1223 RA cases and 1090 controls. Results Fourteen SNP in the STAT3 and STAT1-STAT4 loci were associated with anticitrullinated protein antibody (ACPA)-negative RA in the Swedish cohort. Three of the SNP in STAT4 and 2 SNP in STAT3 remained associated with ACPA-negative RA after considering the Spanish results. In addition, rs7574865 and rs10181656, in STAT4, were associated with ACPA-positive RA in the Swedish study. One of these SNP, rs7574865, showed a similar pattern of the association in serologically distinct subgroups of RA in a metaanalysis of all 7 published studies. Conclusion Our findings suggest that variants in STAT genes may contribute differentially to susceptibility to RA in seropositive and in seronegative patients. %U https://www.jrheum.org/content/jrheum/early/2012/06/25/jrheum.111284.full.pdf