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Erschienen in: Neurological Sciences 10/2020

24.04.2020 | Original Article

Mendelian randomization study to evaluate the effects of interleukin-6 signaling on four neurodegenerative diseases

verfasst von: Haihua Zhang, Tao Wang, Zhifa Han, Guiyou Liu

Erschienen in: Neurological Sciences | Ausgabe 10/2020

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Abstract

Background

Multiple sclerosis (MS) is a complex neurological disease and chronic inflammatory disease. Until now, observational studies have reported positive association between serum interleukin-6 (IL-6) levels and MS risk. In order to develop effective therapies, we should establish the causal link between IL-6 signaling and MS. However, it is currently unknown whether IL-6 signaling is causally associated with the risk of MS.

Methods

Here, we selected the increased soluble IL-6R (s-IL-6R) levels as the indirect markers for reduced IL-6 signaling, and performed a Mendelian randomization (MR) study using the rs2228145 variant as the instrumental variable to evaluate and quantify the effect of IL-6 signaling on the risk of MS. To be a comparison, we also evaluated the causal association of IL-6 signaling with the risk of other three neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS).

Results

We found that the increased s-IL-6R levels (per 1 standard deviation) were significantly associated with decreased MS risk (OR = 0.96, 95% CI 0.94–0.98, P = 1.69E-04), but not associated with the risk of AD (OR = 1.01, 95% CI 0.92–1.11, P = 0.835), PD (OR = 0.94, 95% CI 0.84–1.05, P = 0.261), or ALS (OR = 1.00, 95% CI 0.92–1.10, P = 0.9411).

Conclusion

Our findings have the similar directional effects to an existing humanized anti-IL-6R monoclonal antibody Tocilizumab which could bind to the IL-6 binding site of human IL-6R and competitively inhibit IL-6 signaling. Hence, we provided genetic evidence that inhibiting the IL-6 signaling such as tocilizumab treatment might represent a novel therapy for MS.
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Metadaten
Titel
Mendelian randomization study to evaluate the effects of interleukin-6 signaling on four neurodegenerative diseases
verfasst von
Haihua Zhang
Tao Wang
Zhifa Han
Guiyou Liu
Publikationsdatum
24.04.2020
Verlag
Springer International Publishing
Erschienen in
Neurological Sciences / Ausgabe 10/2020
Print ISSN: 1590-1874
Elektronische ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-020-04381-x

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