tetano
Editor, Senior Moderator
Signal Transduct Target Ther
. 2022 Apr 2;7(1):112.
doi: 10.1038/s41392-022-00923-1.
A genetic variant in IL-6 lowering its expression is protective for critical patients with COVID-19
Bo Gong[SUP] #[/SUP][SUP] 1 2 3 4 [/SUP], Lulin Huang[SUP] #[/SUP][SUP] 2 3 4 [/SUP], Yongquan He[SUP] #[/SUP][SUP] 1 2 3 4 [/SUP], Wen Xie[SUP] #[/SUP][SUP] 5 6 [/SUP], Yi Yin[SUP] 2 4 [/SUP], Yi Shi[SUP] 2 3 4 [/SUP], Jialing Xiao[SUP] 2 [/SUP], Ling Zhong[SUP] 2 3 4 [/SUP], Yi Zhang[SUP] 2 3 4 [/SUP], Zhilin Jiang[SUP] 2 3 4 [/SUP], Fang Hao[SUP] 2 3 [/SUP], Yu Zhou[SUP] 2 3 4 [/SUP], Huan Li[SUP] 2 [/SUP], Li Jiang[SUP] 2 3 [/SUP], Xingxiang Yang[SUP] 7 [/SUP], Xiangrong Song[SUP] 8 [/SUP], Yan Kang[SUP] 8 [/SUP], Lin Tuo[SUP] 7 [/SUP], Yi Huang[SUP] 2 3 [/SUP], Ping Shuai[SUP] 1 [/SUP], Yuping Liu[SUP] 1 [/SUP], Fang Zheng[SUP] 9 [/SUP], Zhenglin Yang[SUP] 10 11 12 [/SUP]
Affiliations
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[SUP]-15[/SUP], 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[SUP]-3[/SUP], OR = 0.67). This variant surpassed the formal threshold for genome-wide significance (combined p = 4.64 × 10[SUP]-16[/SUP], 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.
. 2022 Apr 2;7(1):112.
doi: 10.1038/s41392-022-00923-1.
A genetic variant in IL-6 lowering its expression is protective for critical patients with COVID-19
Bo Gong[SUP] #[/SUP][SUP] 1 2 3 4 [/SUP], Lulin Huang[SUP] #[/SUP][SUP] 2 3 4 [/SUP], Yongquan He[SUP] #[/SUP][SUP] 1 2 3 4 [/SUP], Wen Xie[SUP] #[/SUP][SUP] 5 6 [/SUP], Yi Yin[SUP] 2 4 [/SUP], Yi Shi[SUP] 2 3 4 [/SUP], Jialing Xiao[SUP] 2 [/SUP], Ling Zhong[SUP] 2 3 4 [/SUP], Yi Zhang[SUP] 2 3 4 [/SUP], Zhilin Jiang[SUP] 2 3 4 [/SUP], Fang Hao[SUP] 2 3 [/SUP], Yu Zhou[SUP] 2 3 4 [/SUP], Huan Li[SUP] 2 [/SUP], Li Jiang[SUP] 2 3 [/SUP], Xingxiang Yang[SUP] 7 [/SUP], Xiangrong Song[SUP] 8 [/SUP], Yan Kang[SUP] 8 [/SUP], Lin Tuo[SUP] 7 [/SUP], Yi Huang[SUP] 2 3 [/SUP], Ping Shuai[SUP] 1 [/SUP], Yuping Liu[SUP] 1 [/SUP], Fang Zheng[SUP] 9 [/SUP], Zhenglin Yang[SUP] 10 11 12 [/SUP]
Affiliations
- PMID: 35368020
- DOI: 10.1038/s41392-022-00923-1
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[SUP]-15[/SUP], 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[SUP]-3[/SUP], OR = 0.67). This variant surpassed the formal threshold for genome-wide significance (combined p = 4.64 × 10[SUP]-16[/SUP], 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.