PT  - JOURNAL ARTICLE
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
TI  - Variants Within STAT Genes Reveal Association with Anticitrullinated Protein Antibody-negative Rheumatoid Arthritis in 2 European Populations
AID  - 10.3899/jrheum.111284
DP  - 2012 Aug 01
TA  - The Journal of Rheumatology
PG  - 1509--1516
VI  - 39
IP  - 8
4099  - http://www.jrheum.org/content/39/8/1509.short
4100  - http://www.jrheum.org/content/39/8/1509.full
SO  - J Rheumatol2012 Aug 01; 39
AB  - 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.