Frontiers in Immunology (Sep 2021)
Genetic Associations Between IL-6 and the Development of Autoimmune Arthritis Are Gender-Specific
- Jianqiao Hong,
- Jianqiao Hong,
- Jianqiao Hong,
- Zihao Qu,
- Zihao Qu,
- Zihao Qu,
- Xiaoxiao Ji,
- Xiaoxiao Ji,
- Xiaoxiao Ji,
- Congsun Li,
- Congsun Li,
- Congsun Li,
- Geng Zhang,
- Geng Zhang,
- Geng Zhang,
- Ciliang Jin,
- Jie Wang,
- Jie Wang,
- Jie Wang,
- Yongxing Zhang,
- Yongxing Zhang,
- Yongxing Zhang,
- Yue Shen,
- Yue Shen,
- Yue Shen,
- Jiahong Meng,
- Jiahong Meng,
- Jiahong Meng,
- Chenhe Zhou,
- Chenhe Zhou,
- Chenhe Zhou,
- Chaohua Fang,
- Wei Wang,
- Wei Wang,
- Wei Wang,
- Shigui Yan,
- Shigui Yan,
- Shigui Yan
Affiliations
- Jianqiao Hong
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Jianqiao Hong
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Jianqiao Hong
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China
- Zihao Qu
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zihao Qu
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Zihao Qu
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China
- Xiaoxiao Ji
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Xiaoxiao Ji
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Xiaoxiao Ji
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China
- Congsun Li
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Congsun Li
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Congsun Li
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China
- Geng Zhang
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Geng Zhang
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Geng Zhang
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China
- Ciliang Jin
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Jie Wang
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Jie Wang
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Jie Wang
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China
- Yongxing Zhang
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Yongxing Zhang
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Yongxing Zhang
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China
- Yue Shen
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Yue Shen
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Yue Shen
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China
- Jiahong Meng
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Jiahong Meng
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Jiahong Meng
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China
- Chenhe Zhou
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Chenhe Zhou
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Chenhe Zhou
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China
- Chaohua Fang
- Joint Surgery, Ningbo 6th Hospital, Ningbo, China
- Wei Wang
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Wei Wang
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Wei Wang
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China
- Shigui Yan
- Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Shigui Yan
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Shigui Yan
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China
- DOI
- https://doi.org/10.3389/fimmu.2021.707617
- Journal volume & issue
-
Vol. 12
Abstract
ObjectivesTo find out the genetic association between IL6 and autoimmune arthritis.MethodsWe performed a two-sample Mendelian randomization (MR) study using multiple genome-wide association studies (GWAS) datasets. Furthermore, a sex-stratified MR study was performed to identify sexual dimorphism in the association between IL6 and autoimmune arthritis. Then, LocusZoom plots were displayed based on the IL6R gene region to present evidence of genetic colocalization between diseases.ResultsThe MR result denoted a genetic association between the increased level of IL-6 signaling and risk of RA (β=0.325, 95%CI 0.088, 0.561, p=7.08E-03) and AS (β=1.240, 95%CI 0.495, 1.980, p=1.1E-03). Accordingly, sIL6R was found to have negatively correlation with the onset of RA (β=-0.020, 95%CI -0.0320, -0.008, p=1.18E-03) and AS (β=-0.125, 95%CI -0.177, -0.073, p=2.29E-06). However, no genetic association between IL6/sIL6R and PsA was detected. The gender-stratified MR analysis showed that IL6 was associated with AS in the male population, with RA in the female population, and with PsA in the male population. Additionally, ADAR, a gene identified by a sensitive test, could be the reason for the nonsignificant association between IL6 and PsA in a pooled population.ConclusionOur findings showed that the overactive IL6 signal pathway led to autoimmune arthritis, especially in RA and AS. Sexual difference was also observed in IL6-intermediate susceptibility to autoimmune arthritis.
Keywords
