RT Journal Article
SR Electronic
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
FD The Journal of Rheumatology
SP 1509
OP 1516
DO 10.3899/jrheum.111284
VO 39
IS 8
A1 MARIA SEDDIGHZADEH
A1 ANTONIO GONZALEZ
A1 BO DING
A1 AIDA FERREIRO-IGLESIAS
A1 JUAN J. GOMEZ-REINO
A1 Rheumatoid Arthritis Network and Coordinated Project
A1 LARS KLARESKOG
A1 LARS ALFREDSSON
A1 KYRI DUNUSSI-JOANNOPOULOS
A1 JAMES D. CLARK
A1 LEONID PADYUKOV
YR 2012
UL http://www.jrheum.org/content/39/8/1509.abstract
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.