A genetic variant in IL-6 lowering its expression is protective for critical patients with COVID-19
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 cri...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-04-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-022-00923-1 |
| _version_ | 1819052416003211264 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Bo Gong |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T12:19:29Z |
| format | Article |
| id | doaj.art-876eaf3a65cf4e2b9ea068010a0aba4c |
| institution | Directory Open Access Journal |
| issn | 2059-3635 |
| language | English |
| last_indexed | 2024-12-21T12:19:29Z |
| publishDate | 2022-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj.art-876eaf3a65cf4e2b9ea068010a0aba4c2022-12-21T19:04:21ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352022-04-01711710.1038/s41392-022-00923-1A genetic variant in IL-6 lowering its expression is protective for critical patients with COVID-19Bo Gong0Lulin Huang1Yongquan He2Wen Xie3Yi Yin4Yi Shi5Jialing Xiao6Ling Zhong7Yi Zhang8Zhilin Jiang9Fang Hao10Yu Zhou11Huan Li12Li Jiang13Xingxiang Yang14Xiangrong Song15Yan Kang16Lin Tuo17Yi Huang18Ping Shuai19Yuping Liu20Fang Zheng21Zhenglin Yang22Department of Health Management, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaSichuan 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 ChinaDepartment of Health Management, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaCenter for Gene Diagnosis & Department of Laboratory Medicine, Zhongnan Hospital of Wuhan UniversitySichuan 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 ChinaSichuan 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 ChinaSichuan 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 ChinaSichuan 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 ChinaSichuan 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 ChinaSichuan 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 ChinaSichuan 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 ChinaSichuan 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 ChinaSichuan 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 ChinaSichuan 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 ChinaInfectious Disease Department, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaDepartment of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityInfectious Disease Department, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaSichuan 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 ChinaDepartment of Health Management, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaDepartment of Health Management, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaCenter for Gene Diagnosis & Department of Laboratory Medicine, Zhongnan Hospital of Wuhan UniversitySichuan 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 ChinaAbstract 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.https://doi.org/10.1038/s41392-022-00923-1 |
| spellingShingle | 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 A genetic variant in IL-6 lowering its expression is protective for critical patients with COVID-19 Signal Transduction and Targeted Therapy |
| title | A genetic variant in IL-6 lowering its expression is protective for critical patients with COVID-19 |
| title_full | A genetic variant in IL-6 lowering its expression is protective for critical patients with COVID-19 |
| title_fullStr | A genetic variant in IL-6 lowering its expression is protective for critical patients with COVID-19 |
| title_full_unstemmed | A genetic variant in IL-6 lowering its expression is protective for critical patients with COVID-19 |
| title_short | A genetic variant in IL-6 lowering its expression is protective for critical patients with COVID-19 |
| title_sort | genetic variant in il 6 lowering its expression is protective for critical patients with covid 19 |
| url | https://doi.org/10.1038/s41392-022-00923-1 |
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