Zhang Jixiang, Wu Jianhong, Peng Xiulan, Song Jia, Wang Jun, Dong Weiguo
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
Wuhan medical treatment center, Wuhan, Hubei Province, China.
PLoS One. 2014 Oct 6;9(10):e109625. doi: 10.1371/journal.pone.0109625. eCollection 2014.
Many studies have investigated the associations between the signal transducer and activator of transcription 3 (STAT3) in the susceptibility to ulcerative colitis (UC) and Crohn's disease (CD). However, the results remain inconsistent. This meta-analysis determined the risk of STAT3 rs744166 polymorphism-conferred UC and CD susceptibility.
Electronic databases, including PubMed, EMBASE and the Cochrane Library, were searched for all eligible studies that evaluated the association between STAT3 rs744166 polymorphisms with UC and CD risk up to August 21, 2014. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using fixed- or random-effects models.
Twelve studies containing 10298 patients with CD, 4244 patients with UC and 11191 controls were included in this meta-analysis. The results indicated that the STAT3 rs744166 polymorphism was associated with CD and UC susceptibility (CD: GA+AA vs. GG, OR = 1.20, 95%CI, 1.11-1.30, I2 = 0%, Punadjusted<0.00001, PBonferroni<0.00005, PFDR<0.00001; UC: GA+AA vs. GG, OR = 1.21, 95%CI, 1.08-1.36, I2 = 1%, Punadjusted = 0.001, PBonferroni = 0.005, PFDR = 0.00125). In subgroup analyses by ethnicity, the significant association was found only among Caucasians. However, when grouped by age of onset, positive associations were found both among adults and children. In addition, when stratified by study design and genotyping methods, the risk of CD was significantly associated with the STAT3 rs744166 polymorphism in hospital-based and population-based groups and in SNP Array and SNPlex groups. For UC, significant associations were also found in population-based, PCR-RFLP and SNPlex groups. Moreover, these findings were sufficiently robust to withstand the Bonferroni correction and false discovery rate (FDR).
This meta-analysis indicates that carriers of the STAT3 rs744166 'A' allele have a significantly greater risk of CD and UC, especially among Caucasians.
许多研究调查了信号转导子与转录激活子3（STAT3）在溃疡性结肠炎（UC）和克罗恩病（CD）易感性中的关联。然而，结果仍不一致。本荟萃分析确定了STAT3 rs744166多态性导致UC和CD易感性的风险。
检索电子数据库，包括PubMed、EMBASE和Cochrane图书馆，以查找所有评估截至2014年8月21日STAT3 rs744166多态性与UC和CD风险之间关联的合格研究。使用固定效应或随机效应模型计算合并优势比（OR）和95%置信区间（95%CI）。
本荟萃分析纳入了12项研究，共10298例CD患者、4244例UC患者和11191例对照。结果表明，STAT3 rs744166多态性与CD和UC易感性相关（CD：GA + AA vs. GG，OR = 1.20，95%CI，1.11 - 1.30，I2 = 0%，未校正P<0.00001，Bonferroni校正P<0.00005，FDR校正P<0.00001；UC：GA + AA vs. GG，OR = 1.21，95%CI，1.08 - 1.36，I2 = 1%，未校正P = 0.001，Bonferroni校正P = 0.005，FDR校正P = 0.00125）。在按种族进行的亚组分析中，仅在白种人中发现显著关联。然而，按发病年龄分组时，在成人和儿童中均发现了正相关。此外，按研究设计和基因分型方法分层时，在基于医院和基于人群的组以及SNP Array和SNPlex组中，CD风险与STAT3 rs744166多态性显著相关。对于UC，在基于人群的、PCR - RFLP和SNPlex组中也发现了显著关联。而且，这些发现具有足够的稳健性，能够经受住Bonferroni校正和错误发现率（FDR）的检验。
本荟萃分析表明，STAT3 rs744166“A”等位基因携带者患CD和UC的风险显著更高，尤其是在白种人中。
