Barts-MS Journal Club 28-Sept-2020

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The following is our journal club from 28th September and was presented by Dr Ben Jacobs.

Briggs et al. Nicotinic acetylcholine receptors α7 and α9 modifies tobacco smoke risk for multiple sclerosis. MSJ First Published September 14, 2020 Research Article https://doi.org/10.1177/1352458520958361

Introduction: Tobacco smoke exposure is an established risk factor for multiple sclerosis (MS), yet how it confers risk is not known. Evidence from observational studies suggests nicotine may be a protective component. Animal studies further support this hypothesis, demonstrating nicotine’s protective effect in MS is mediated by the presence and absence of α7 and α9 nicotinic acetylcholine receptors (nAChRs), respectively.

Objective: To determine if variation in the genes encoding α7 and α9 nAChRs (cholinergic receptor nicotinic alpha 7 (CHRNA7) and alpha 9 (CHRNA9)) will modify MS risk conferred by tobacco smoking.

Methods: A multi-stage gene-environment (G×E) framework was utilized, including a case–control analysis (286 cases, 176 controls) with haplotype- and gene-based analyses, followed by an extension case-only (1053 cases) analysis for overlapping variants.

Results: The results suggest that CHRNA7 and CHRNA9 modifies MS risk conferred by tobacco smoke, where risk among smokers was increased in carriers of the minor CHRNA9 haplotype and in non-carriers the minor CHRNA7 haplotype. The findings are consistent with the pharmacology of these receptors and animal studies of MS.

Conclusion: This study implicates novel processes in MS initiation and demonstrate the need for further G×E studies to advancing our understanding of the missing heritability of MS.

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4 comments

  • This brings up really interesting questions. Medicinal cannabis is advocated as a treatment for MS. This it typically ‘vaped’ through a device that heats the flower to up to 220 degrees centigrade. Or taken orally was oil. 1. Could vaping tobacco be protective? 2. Would smoking cannabis be detrimental like smoking tobacco. THC and CBD are advocated to treat increased tone in MS, but could they also have an immune effect?

    • 1. Maybe. Nicotine has long been thought to be neuroprotective.
      2. Yes, smoking is a no-no. It is possible to see immune effects (immunosuppression) experimentally but in practice in humans, no as the doses of THC (not CBD) necessary to produce such an effect would leave the subject permanently incapacitated. Definitely a neuroprotective potental though, which is why we really need another trial to answer this question once and for all.
      We’ve published extensively on this over 20 years.

  • Excellent discussion that was well facilitated. My favorite part of these sessions is listening to the group question the structure of the studies being reviewed. Makes me laugh every time. Glad to see the “Journal Club” back in the rotation of blog posts.

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