| Title | Mendelian randomization study to evaluate the effects of interleukin-6 signaling on four neurodegenerative diseases |
| Authors | Zhang, Haihua Wang, Tao Han, Zhifa Liu, Guiyou |
| Affiliation | Capital Med Univ, Xuanwu Hosp, Natl Engn Lab Internet Med Diag & Treatment Techn, Beijing 100053, Peoples R China Capital Med Univ, Beijing Inst Brain Disorders, Beijing, Peoples R China Peking Univ, Acad Adv Interdisciplinary Studies, Beijing, Peoples R China Chinese Inst Brain Res, Beijing, Peoples R China Tsinghua Univ, THU PKU Ctr Life Sci, Sch Med, Sch Pharmaceut Sci, Beijing, Peoples R China Chinese Acad Med Sci, Inst Basic Med Sci, State Key Lab Med Mol Biol, Beijing, Peoples R China Peking Union Med Coll, Dept Pathophysiol, Beijing, Peoples R China Capital Med Univ, Xuanwu Hosp, Dept Neurol, Room 1037,Guanganmennei St, Beijing 100053, Peoples R China |
| Keywords | ANTI-IL-6 RECEPTOR ANTIBODY MULTIPLE-SCLEROSIS PATIENTS GENOME-WIDE ASSOCIATION CORONARY-HEART-DISEASE ALZHEIMERS-DISEASE METAANALYSIS TOCILIZUMAB EXPRESSION LOCI IL-6 |
| Issue Date | Apr-2020 |
| Publisher | NEUROLOGICAL SCIENCES |
| 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. |
| URI | http://hdl.handle.net/20.500.11897/606717 |
| ISSN | 1590-1874 |
| DOI | 10.1007/s10072-020-04381-x |
| Indexed | SCI(E) Scopus |
| Appears in Collections: | 前沿交叉学科研究院 |
