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J Rheumatol. 2012 Aug;39(8):1509-16. doi: 10.3899/jrheum.111284. Epub 2012 Jul 1.

Variants within STAT genes reveal association with anticitrullinated protein antibody-negative rheumatoid arthritis in 2 European populations.

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  • 1Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.



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).


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.


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.


Our findings suggest that variants in STAT genes may contribute differentially to susceptibility to RA in seropositive and in seronegative patients.

[PubMed - indexed for MEDLINE]
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