Association of CCR6 functional polymorphisms with Primary Biliary Cholangitis

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

doi:10.1016/j.jtauto.2024.100234

Association of CCR6 functional polymorphisms with Primary Biliary Cholangitis

J Transl Autoimmun. 2024 Feb 15:8:100234. doi: 10.1016/j.jtauto.2024.100234. eCollection 2024 Jun.

Authors

Mingming Zhang¹, Zhuye Qin², Yexi Huang¹, Wenyan Tian³, You Li⁴, Chan Wang⁵, Weifeng Zhao⁶, Yaping Dai⁷, Xingjuan Shi¹, M Eric Gershwin⁸, Xiong Ma⁴, Meilin Wang⁹, Xiangdong Liu¹, Weichang Chen³, Fang Qiu¹⁰

Affiliations

¹ Key Laboratory of Developmental Genes and Human Diseases, School of Life Science and Technology, Southeast University, Nanjing, Jiangsu, 210096, China.
² Department of Laboratory Medicine, Southeast University Hospital, Southeast University, Nanjing, Jiangsu, 210096, China.
³ Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China.
⁴ Department of Gastroenterology and Hepatology, Shanghai Institute of Digestive Diseases, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, 200001, China.
⁵ Institute of Translational Medicine, Yangzhou University Medical College, Yangzhou, Jiangsu, 225009, China.
⁶ Department of Hepatology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China.
⁷ Department of Laboratory Medicine, The Fifth People's Hospital of Wuxi, Wuxi, Jiangsu, 214000, China.
⁸ Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA, 95616, USA.
⁹ Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, Nanjing Medical University School of Public Health, Nanjing, Jiangsu, 210029, China.
¹⁰ Department of Laboratory Medicine, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210031, China.

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.

Keywords: CC chemokine ligand 20; CC chemokine receptor 6; Han Chinese; Primary biliary cholangitis; Single nucleotide polymorphism.