Smoking, cardiovascular risk factors and LRP2 gene variation: Associations with disease severity, cognitive function and brain structure in primary progressive multiple sclerosis

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Background: Smoking, cardiovascular risk factors, and genetic factors can have adverse effects in MS. Objective: To determine if smoking after disease onset, cardiovascular risk factors, and genetic variants influence primary progressive MS (PPMS). Method: In this cross-sectional study, smoking habits, Framingham Risk Score (FRS), genetic variants, including the low-density lipoprotein receptor-related protein 2 (LRP2) SNP rs12988804 and MRI were collected in 60 PPMS trial participants. Disability and cognition were assessed with the Age-Related Multiple Sclerosis Severity (ARMSS) score, the Progressive-Onset MS Multiple Sclerosis Severity Score, and the Brief International Cognitive Assessment for MS. Results: Smoking after PPMS onset was significantly associated with higher ARMSS (95% CI 0.8–2.4, p = 0.00016) statistically significant after Bonferroni correction. Lower magnetization transfer ratio in lesions was also significantly associated with smoking after onset of PPMS after correction (95% CI -0.9–-4.4, p = 0.0035). Pack-years in people who smoked after onset was likewise significantly associated with higher ARMSS score (b = 0.06 95% CI 0.02–0.09, p = 0.0021) as well as lower Symbol Digit Modalities Test scores (b = -0.40; 95% CI -0.66–-0.13, p = 0.0037), both statistically significant after Bonferroni correction. The LRP2 risk allele was associated with decreased performance on the California Verbal Learning Test 2 after correction (CC vs. CT+TT 95% CI -14.2–-3.4, p = 0.0018). Conclusion: If validated, these findings suggest that intervention regarding smoking may be beneficial in PPMS. If confirmed, assessment of the LRP2 gene variant may aid in the understanding of underlying pathological mechanisms in PPMS.

OriginalsprogEngelsk
Artikelnummer103296
TidsskriftMultiple Sclerosis and Related Disorders
Vol/bind56
ISSN2211-0348
DOI
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
Henrik Lundell has received funding from the European Research Council ( ERC ) under the European Union's Horizon 2020 research and innovation program (Grant agreement no. 804746 ).

Funding Information:
H H?jsgaard Chow reports non-financial support from Merck, non-financial support from Teva, non-financial support from Biogen, non-financial support from Roche, outside the submitted work; J Talbot reports non-financial support from Sanofi Genzyme, outside the submitted work; L Marstrand reports grants from Novartis, personal fees from Biogen, outside the submitted work; H Lundell has a patent for performing diffusion weighted magnetic resonance measurements on a sample pending to RWI AB; Dr. Siebner reports personal fees from Sanofi Genzyme, personal fees from Springer Publishers, personal fees from Elsevier Publishers, personal fees from Lundbeck AS, personal fees from Gyldendal Publishers, grants from Lundbeck Foundation, outside the submitted work; H Bach S?ndergaard reports no conflicts of interest; Dr. Sellebjerg reports grants from Biogen, grants from Danish Multiple Sclerosis Society, during the conduct of the study; grants and personal fees from Biogen, personal fees from Lundbeck, grants and personal fees from Merck, grants and personal fees from Novartis, grants and personal fees from Roche, grants and personal fees from Sanofi Genzyme, outside the submitted work; and Dr. Sellebjerg is section editor on Multiple Sclerosis and Related Disorders.This study was supported by grants from Biogen and the Danish Multiple Sclerosis Society (Grant nos. A33491, A35741 and A38444). These entities were not involved in the conduct, data collection or data analysis or interpretation of the results of the study. Hartwig R. Siebner holds a 5-year professorship in precision medicine at the Faculty of Health Sciences and Medicine, University of Copenhagen which is sponsored by the Lundbeck Foundation (Grant no. R186-2015-2138). Henrik Lundell has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (Grant agreement no. 804746). We want to thank laboratory technician Linda Wolter Christensen for her excellent work on the genetic analyses for this paper. We thank Antoine Lutti, Nikolaus Weiskopf and Gunther Helms for kindly providing the MRI sequence used for mapping MTR.

Funding Information:
Hartwig R. Siebner holds a 5-year professorship in precision medicine at the Faculty of Health Sciences and Medicine, University of Copenhagen which is sponsored by the Lundbeck Foundation (Grant no. R186-2015-2138 ).

Funding Information:
This study was supported by grants from Biogen and the Danish Multiple Sclerosis Society (Grant nos. A33491 , A35741 and A38444 ). These entities were not involved in the conduct, data collection or data analysis or interpretation of the results of the study.

Publisher Copyright:
© 2021 The Author(s)

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