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A genetic variant in IL-6 lowering its expression is protective for critical patients with COVID-19.
Gong, Bo; Huang, Lulin; He, Yongquan; Xie, Wen; Yin, Yi; Shi, Yi; Xiao, Jialing; Zhong, Ling; Zhang, Yi; Jiang, Zhilin; Hao, Fang; Zhou, Yu; Li, Huan; Jiang, Li; Yang, Xingxiang; Song, Xiangrong; Kang, Yan; Tuo, Lin; Huang, Yi; Shuai, Ping; Liu, Yuping; Zheng, Fang; Yang, Zhenglin.
  • Gong B; Department of Health Management, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
  • Huang L; 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, Chengdu, Sichuan, China.
  • He Y; Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
  • Xie W; Institute of Chengdu Biology, Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, Sichuan, China.
  • Yin Y; 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, Chengdu, Sichuan, China.
  • Shi Y; Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
  • Xiao J; Institute of Chengdu Biology, Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, Sichuan, China.
  • Zhong L; Department of Health Management, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
  • Zhang Y; 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, Chengdu, Sichuan, China.
  • Jiang Z; Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
  • Hao F; Institute of Chengdu Biology, Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, Sichuan, China.
  • Zhou Y; Center for Gene Diagnosis & Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • Li H; Department of Laboratory Medicine, Wuhan Leishenshan Hospital, Wuhan, Hubei, China.
  • Jiang L; 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, Chengdu, Sichuan, China.
  • Yang X; Institute of Chengdu Biology, Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, Sichuan, China.
  • Song X; 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, Chengdu, Sichuan, China.
  • Kang Y; Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
  • Tuo L; Institute of Chengdu Biology, Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, Sichuan, China.
  • Huang Y; 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, Chengdu, Sichuan, China.
  • Shuai P; 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, Chengdu, Sichuan, China.
  • Liu Y; Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
  • Zheng F; Institute of Chengdu Biology, Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, Sichuan, China.
  • Yang Z; 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, Chengdu, Sichuan, China.
Signal Transduct Target Ther ; 7(1): 112, 2022 04 02.
Article in English | MEDLINE | ID: covidwho-1773956
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Interleukin-6 / COVID-19 Type of study: Cohort study / Observational study / Prognostic study Topics: Variants Limits: Humans / Male Language: English Journal: Signal Transduct Target Ther Year: 2022 Document Type: Article Affiliation country: S41392-022-00923-1

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Interleukin-6 / COVID-19 Type of study: Cohort study / Observational study / Prognostic study Topics: Variants Limits: Humans / Male Language: English Journal: Signal Transduct Target Ther Year: 2022 Document Type: Article Affiliation country: S41392-022-00923-1