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Replication study and meta-analysis indicate a suggestive association of RUNX3 locus with primary biliary cholangitis
Immunogenetics ( IF 3.2 ) Pub Date : 2020-12-07 , DOI: 10.1007/s00251-020-01192-4
Rohil Jawed , Mingming Zhang , Chan Wang , Shu-Han Yang , Peng Jiang , Qiuyuan Wu , Li Li , Weichang Chen , M. Eric Gershwin , Ye Tian , Michael F. Seldin , Xiong Ma , Xiangdong Liu , Zhe-Xiong Lian , Xingjuan Shi

Susceptibility to primary biliary cholangitis (PBC) is in part genetically determined. In our previous PBC genome-wide association study (GWAS) in 1118 Han Chinese PBC and 4036 controls, we noted that multiple SNPs in the runt-related transcription factor 3 (RUNX3) regions showed a nominally significant association. The tag SNP rs7529070 was genotyped using a TaqMan assay in a separately collected 1435 PBC and 3205 controls. A meta-analysis with a combined 2553 PBC and 7241 controls showed that rs7529070 is still nominally associated with PBC (p = 1.7 × 10–4, odds ratio (OR) = 1.18, 95% confidence interval (CI) = 1.08–1.28). Further analysis indicated that the risk allele of rs7529070 (G allele) is in complete linkage disequilibrium (LD) (r2 = 1) with the G allele of rs4648889, which is known to be associated with increased RUNX3 expression. Bioinformatic analysis with existing expression data showed that the expression of RUNX3 is significantly increased in PBC patients (p = 0.001) and the expression level is correlated with disease severity. Consistently, we also found significantly increased RUNX3 expression (p < 0.01) in the livers of dnTGFβRII mice (a PBC mouse model). This study suggests that the RUNX3 locus may associate with PBC in Han Chinese.



中文翻译:

复制研究和荟萃分析表明RUNX3基因座与原发性胆源性胆管炎的暗示关联

原发性胆源性胆管炎(PBC)的易感性部分是由基因决定的。在我们先前的1118个汉族PBC和4036个对照的PBC全基因组关联研究(GWAS)中,我们注意到与矮子相关的转录因子3(RUNX3)区域中的多个SNP表现出名义上的显着关联。使用TaqMan分析在分别收集的1435 PBC和3205对照中对标签SNP rs7529070进行基因分型。结合2553个PBC和7241个控件的荟萃分析显示,rs7529070仍名义上与PBC相关(p  = 1.7×10 –4,优势比(OR)= 1.18,95%置信区间(CI)= 1.08-1.28) 。进一步的分析表明,rs7529070的风险等位基因(G等位基因)处于完全连锁不平衡(LD)(r2  = 1)带有rs4648889的G等位基因,已知与RUNX3表达增加有关。利用现有表达数据进行的生物信息学分析表明,RUNX3的表达在PBC患者中显着增加(p  = 0.001),且表达水平与疾病严重程度相关。一致地,我们还发现dnTGFβRII小鼠(PBC小鼠模型) 的肝脏中RUNX3表达显着增加(p <0.01 )。这项研究表明,RUNX3基因座可能与汉族人的PBC有关。

更新日期:2020-12-07
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