A genetic variant in IL-6 lowering its expression is protective for critical patients with COVID-19

Bo Gong; Lulin Huang; Yongquan He; Wen Xie; Yi Yin; Yi Shi; Jialing Xiao; Ling Zhong; Yi Zhang; Zhilin Jiang; Fang Hao; Yu Zhou; Huan Li; Li Jiang; Xingxiang Yang; Xiangrong Song; Yan Kang; Lin Tuo; Yi Huang; Ping Shuai; Yuping Liu; Fang Zheng; Zhenglin Yang

doi:10.1038/s41392-022-00923-1

Signal Transduction and Targeted Therapy (Apr 2022)

A genetic variant in IL-6 lowering its expression is protective for critical patients with COVID-19

Bo Gong,
Lulin Huang,
Yongquan He,
Wen Xie,
Yi Yin,
Yi Shi,
Jialing Xiao,
Ling Zhong,
Yi Zhang,
Zhilin Jiang,
Fang Hao,
Yu Zhou,
Huan Li,
Li Jiang,
Xingxiang Yang,
Xiangrong Song,
Yan Kang,
Lin Tuo,
Yi Huang,
Ping Shuai,
Yuping Liu,
Fang Zheng,
Zhenglin Yang

Affiliations

Bo Gong: Department of Health Management, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Lulin Huang: Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Department of laboratory medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Yongquan He: Department of Health Management, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Wen Xie: Center for Gene Diagnosis & Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University
Yi Yin: Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Department of laboratory medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Yi Shi: Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Department of laboratory medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Jialing Xiao: Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Department of laboratory medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Ling Zhong: Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Department of laboratory medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Yi Zhang: Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Department of laboratory medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Zhilin Jiang: Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Department of laboratory medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Fang Hao: Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Department of laboratory medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Yu Zhou: Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Department of laboratory medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Huan Li: Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Department of laboratory medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Li Jiang: Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Department of laboratory medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Xingxiang Yang: Infectious Disease Department, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Xiangrong Song: Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University
Yan Kang: Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University
Lin Tuo: Infectious Disease Department, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Yi Huang: Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Department of laboratory medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Ping Shuai: Department of Health Management, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Yuping Liu: Department of Health Management, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Fang Zheng: Center for Gene Diagnosis & Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University
Zhenglin Yang: Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Department of laboratory medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China

DOI: https://doi.org/10.1038/s41392-022-00923-1
Journal volume & issue: Vol. 7, no. 1
pp. 1 – 7

Abstract

Read online

Abstract Critical coronavirus disease 2019 (COVID-19) is associated with high mortality and potential genetic factors have been reported to be involved in the development of critical COVID-19. We performed a genome-wide association study to identify the genetic factors responsible for developing critical COVID-19. 632 critical patients with COVID-19 and 3021 healthy controls from the Chinese population were recruited. First, we identified a genome-wide significant difference of IL-6 rs2069837 (p = 9.73 × 10−15, OR = 0.41) between 437 critical patients with COVID-19 and 2551 normal controls in the discovery cohort. When replicated these findings in a set of 195 patients with critical COVID-19 and 470 healthy controls, we detected significant association of rs2069837 with COVID-19 (p = 8.89 × 10−3, OR = 0.67). This variant surpassed the formal threshold for genome-wide significance (combined p = 4.64 × 10−16, OR = 0.49). Further analysis revealed that there was a significantly stronger expression of IL-6 in the serum from patients with critical COVID-19 than in that from patients with asymptomatic COVID-19. An in vitro assay showed that the A to G allele changes in rs2069837 within IL-6 obviously decreased the luciferase expression activity. When analyzing the effect of this variant on the IL-6 in the serum based on the rs2069837 genotype, we found that the A to G variation in rs2069837 decreased the expression of IL-6, especially in the male. Overall, we identified a genetic variant in IL-6 that protects against critical conditions with COVID-19 though decreasing IL-6 expression in the serum.

Published in Signal Transduction and Targeted Therapy

ISSN: 2059-3635 (Online)
Publisher: Nature Publishing Group
Country of publisher: United Kingdom
LCC subjects: Medicine; Science: Biology (General)
Website: http://www.nature.com/sigtrans/

About the journal