STAT4 gene polymorphisms are associated with susceptibility and ANA status in primary biliary cirrhosis.
STAT4 gene polymorphisms are associated with susceptibility and ANA status in primary biliary cirrhosis.
复制标题
DOI：
10.1155/2014/727393
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Ota M
中科院分区：
文献类型：
--
作者：
Joshita S;Umemura T;Nakamura M;Katsuyama Y;Shibata S;Kimura T;Morita S;Komatsu M;Matsumoto A;Yoshizawa K;Ishibashi H;Tanaka E;Ota M
最近的全基因组关联研究表明，遗传因素导致原发性胆汁性肝硬化（PBC）易感性。尽管已有多篇报道证明白细胞介素（IL）12信号通路参与PBC发病机制，但其确切的遗传因素尚未完全阐明。在这里，我们进行了 IL12A、IL12RB 以及信号转导子和转录激活子 4 (STAT4) 遗传变异与 PBC 易感性之间的关联分析。对 395 名 PBC 患者和 458 名日本裔健康受试者进行单核苷酸多态性 (SNP) 基因分型，并评估其与 PBC 易感性、抗核抗体 (ANA) 状态和抗线粒体抗体 (AMA) 状态的关联。我们检测到几个 STAT4 SNP 与 PBC 易感性显着相关（rs10168266；P = 9.4 × 10−3，rs11889341；P = 1.2 × 10−3，rs7574865；P = 4.0 × 10−4，rs8179673；P = 2.0 × 10−4，和rs10181656；P = 4.2 × 10−5)。三个风险等位基因（rs7574865；P = 0.040、rs8179673；P = 0.032 和 rs10181656；P = 0.031）与 ANA 状态相关，但与 AMA 阳性无关。我们的研究结果证实 STAT4 与 PBC 易感性有关，并且可能在日本人群的 ANA 状态中发挥作用。
Recent genome-wide association studies suggest that genetic factors contribute to primary biliary cirrhosis (PBC) susceptibility. Although several reports have demonstrated that the interleukin (IL) 12 signaling pathway is involved in PBC pathogenesis, its precise genetic factors have not been fully clarified. Here, we performed an association analysis between IL12A, IL12RB, and signal transducer and activator of transcription 4 (STAT4) genetic variations and susceptibility to PBC. Single nucleotide polymorphisms (SNPs) were genotyped in 395 PBC patients and 458 healthy subjects of Japanese ethnicity and evaluated for associations with PBC susceptibility, anti-nuclear antibody (ANA) status, and anti-mitochondrial antibody (AMA) status. We detected significant associations with PBC susceptibility for several STAT4 SNPs (rs10168266; P = 9.4 × 10−3, rs11889341; P = 1.2 × 10−3, rs7574865; P = 4.0 × 10−4, rs8179673; P = 2.0 × 10−4, and rs10181656; P = 4.2 × 10−5). Three risk alleles (rs7574865; P = 0.040, rs8179673; P = 0.032, and rs10181656; P = 0.031) were associated with ANA status, but not with AMA positivity. Our findings confirm that STAT4 is involved in PBC susceptibility and may play a role in ANA status in the Japanese population.
登录
查看更多内容
影响因子：
3.7
作者：
Alonso-Perez E;Suarez-Gestal M;Calaza M;Ordi-Ros J;Balada E;Bijl M;Papasteriades C;Carreira P;Skopouli FN;Witte T;Endreffy E;Marchini M;Migliaresi S;Sebastiani GD;Santos MJ;Suarez A;Blanco FJ;Barizzone N;Pullmann R;Ruzickova S;Lauwerys BR;Gomez-Reino JJ;Gonzalez A;European Consortium of SLE DNA Collections
通讯作者：
European Consortium of SLE DNA Collections
影响因子：
6.3
作者：
Inamine, Tatsuo;Nakamura, Minoru;Tsukamoto, Kazuhiro
通讯作者：
Tsukamoto, Kazuhiro
影响因子：
30.8
作者：
通讯作者：
--
全基因组的荟萃分析鉴定了与原发性胆道肝硬化相关的三个基因座。
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
56.9
作者：
Gabriel, SB;Schaffner, SF;Altshuler, D
通讯作者：
Altshuler, D