TY - JOUR

T1 - Smoking, cardiovascular risk factors and LRP2 gene variation

T2 - Associations with disease severity, cognitive function and brain structure in primary progressive multiple sclerosis

AU - Chow, Helene Højsgaard

AU - Talbot, Jacob

AU - Marstrand, Lisbet

AU - Lundell, Henrik

AU - Roman Siebner, Hartwig

AU - Bach Søndergaard, Helle

AU - Sellebjerg, Finn

N1 - Publisher Copyright: © 2021 The Author(s)

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - Age-related multiple sclerosis severity score

KW - Framingham risk score

KW - Low-density lipoprotein receptor-related protein 2

KW - Primary progressive multiple sclerosis

KW - Smoking

U2 - 10.1016/j.msard.2021.103296

DO - 10.1016/j.msard.2021.103296

M3 - Journal article

C2 - 34678704

AN - SCOPUS:85117241062

VL - 56

JO - Multiple Sclerosis and Related Disorders

JF - Multiple Sclerosis and Related Disorders

SN - 2211-0348

M1 - 103296

ER -