| Autor: |
Fergus Hamilton, Ruth E Mitchell, Andrei Constantinescu, David Hughes, Aubrey Cunnington, Peter Ghazal, Nicholas J. Timpson |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
International Journal of Infectious Diseases, Vol 129, Iss , Pp 251-259 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1201-9712 |
| DOI: |
10.1016/j.ijid.2023.02.008 |
| Popis: |
Objectives: Severe malaria remains a deadly disease for many young children in low- and middle-income countries. Levels of interleukin (IL)-6 have been shown to identify cases of severe malaria and associate with severity, but it is unknown if this association is causal. Methods: A single nucleotide polymorphism (SNP; rs2228145) in the IL-6 receptor was chosen as a genetic variant that is known to alter IL-6 signaling. We tested this, then took this forward as an instrument to perform Mendelian randomization (MR) in MalariaGEN, a large cohort study of patients with severe malaria at 11 worldwide sites. Results: In MR analyses using rs2228145, we did not identify an effect of decreased IL-6 signaling on severe malaria (odds ratio 1.14, 95% confidence interval 0.56-2.34, P = 0.713). The estimates of the association with any severe malaria subphenotype were similarly null, although with some imprecision. Further analyses using other MR approaches had similar results. Conclusion: These analyses do not support a causal role for IL-6 signaling in the development of severe malaria. This result suggests IL-6 may not be causal for severe outcomes in malaria, and that therapeutic manipulation of IL-6 is unlikely to be a suitable treatment for severe malaria. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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