Association of CCR6 functional polymorphisms with Primary Biliary Cholangitis

IF 4.7 Q2 IMMUNOLOGY Journal of Translational Autoimmunity Pub Date : 2024-02-15 DOI:10.1016/j.jtauto.2024.100234
Mingming Zhang , Zhuye Qin , Yexi Huang , Wenyan Tian , You Li , Chan Wang , Weifeng Zhao , Yaping Dai , Xingjuan Shi , M. Eric Gershwin , Xiong Ma , Meilin Wang , Xiangdong Liu , Weichang Chen , Fang Qiu
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Abstract

The biliary epithelial cells release CC chemokine receptor 6 (CCR6) ligand 20 (CCL20), leading to recruitment of CCR6+ T cells and subsequent infiltration into the biliary epithelium in primary biliary cholangitis patients. Previous genome-wide multi-national meta-analysis, including our Han Chinese cohort, showed significant association of CCR6 and CCL20 single nucleotide polymorphisms (SNP) with PBC. We report here that significantly associated SNPs, identified in the CCR6 locus based on our Han Chinese genome-wide association study, can be separated into “protective” and “risk” groups, but only “risk” SNPs were confirmed using a separate Han Chinese PBC cohort. Only weak association of CCL20 SNPs was observed in Han Chinese PBC cohorts. Fine-mapping and logistical analysis identified a previously defined functional variant that, leads to increased CCR6 expression, which contributed to increased genetic susceptibility to PBC in Han Chinese cohort.

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CCR6 功能多态性与原发性胆汁性胆管炎的关系
原发性胆汁性胆管炎患者的胆道上皮细胞会释放CC趋化因子受体6(CCR6)配体20(CCL20),导致CCR6+T细胞招募并随后浸润胆道上皮细胞。先前的全基因组多国荟萃分析(包括我们的汉族队列)显示,CCR6 和 CCL20 单核苷酸多态性(SNP)与原发性胆汁性胆管炎有显著相关性。我们在此报告,根据我们的中国汉族全基因组关联研究,在 CCR6 位点上发现的明显相关 SNP 可分为 "保护 "组和 "风险 "组,但只有 "风险 "SNP 通过单独的中国汉族 PBC 队列得到证实。在汉族 PBC 队列中仅观察到 CCL20 SNPs 的弱关联。精细图谱绘制和逻辑分析确定了一个先前定义的功能变异,该变异导致 CCR6 表达增加,从而增加了汉族队列中 PBC 的遗传易感性。
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来源期刊
Journal of Translational Autoimmunity
Journal of Translational Autoimmunity Medicine-Immunology and Allergy
CiteScore
7.80
自引率
2.60%
发文量
33
审稿时长
55 days
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