TY - JOUR T1 - Variants Within STAT Genes Reveal Association with Anticitrullinated Protein Antibody-negative Rheumatoid Arthritis in 2 European Populations JF - The Journal of Rheumatology JO - J Rheumatol SP - 1509 LP - 1516 DO - 10.3899/jrheum.111284 VL - 39 IS - 8 AU - MARIA SEDDIGHZADEH AU - ANTONIO GONZALEZ AU - BO DING AU - AIDA FERREIRO-IGLESIAS AU - JUAN J. GOMEZ-REINO AU - Rheumatoid Arthritis Network and Coordinated Project AU - LARS KLARESKOG AU - LARS ALFREDSSON AU - KYRI DUNUSSI-JOANNOPOULOS AU - JAMES D. CLARK AU - LEONID PADYUKOV Y1 - 2012/08/01 UR - http://www.jrheum.org/content/39/8/1509.abstract N2 - 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. ER -