Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
J Rheumatol. 2012 Aug;39(8):1509-16. doi: 10.3899/jrheum.111284. Epub 2012 Jul 1.
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.
STAT3 和 STAT4 等因素对于白细胞介素 12（IL-12）介导的 Th1 反应、IL-23 信号的传递以及 Th17 细胞的存活和扩增至关重要。我们研究了 STAT3 和 STAT4 多态性与类风湿关节炎（RA）血清学不同亚组之间的关联。
在瑞典的 2043 例 RA 病例和 1115 例对照中，我们研究了 STAT3 和 STAT1-STAT4 基因座内的 41 个单核苷酸多态性（SNP）。在西班牙的 1223 例 RA 病例和 1090 例对照中，对 9 个相关 SNP 进行了检测。
在瑞典队列中，STAT3 和 STAT1-STAT4 基因座中的 14 个 SNP 与抗瓜氨酸蛋白抗体（ACPA）阴性 RA 相关。在考虑西班牙结果后，STAT4 中的 3 个 SNP 和 STAT3 中的 2 个 SNP 仍与 ACPA 阴性 RA 相关。此外，STAT4 中的 rs7574865 和 rs10181656 与瑞典研究中的 ACPA 阳性 RA 相关。这些 SNP 中的一个，rs7574865，在对所有 7 项已发表研究的荟萃分析中，在 RA 的血清学不同亚组中显示出相似的关联模式。
我们的研究结果表明，STAT 基因中的变体可能对血清阳性和血清阴性患者的 RA 易感性有不同的贡献。
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