ArticleInternational journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases2023
The effect of interleukin-6 signaling on severe malaria: A Mendelian randomization analysis.
Article in International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 9 citations in OpenAlex.
- Mendelian Randomization and Infection: Pitfalls and Promises.The Journal of infectious diseases · 2025Review
- Potential of microRNAs as diagnostic markers for distinguishing malaria severity in samples from an Indian cohort.BMC infectious diseases · 2025Article
- Does the Single Nucleotide Polymorphism rs2228145 in IL6R Truly Reflect IL-6 Signaling in Mendelian Randomization Studies?Immune network · 2025Article
- Sacha inchi (Open veterinary journal · 2025Article
- Exploring Biomarkers for Malaria: Advances in Early Detection and Asymptomatic Diagnosis.Biosensors · 2025Review
- Article
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7 authors at 4 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
objectivesSevere 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.
methodsA 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.
resultsIn 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.
conclusionThese 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.
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