Relapsing and Progressive MS Both Impacted by Environmental and Lifestyle Factors

Anna K. Hedstrom, MD, PhD

Using 2 Swedish population-based case-control studies, researchers concluded that both environmental and lifestyle factors are associated with the increased risk of developing multiple sclerosis (MS), both relapsing-onset MS and progressive-onset MS, supporting the notion that the different clinical phenotypes share common underlying disease mechanisms.

Lead author Anna K. Hedstrom, MD, PhD, department of Clinical Neuroscience, Karolinska Institutet, and colleagues aimed to study environmental risk factors and their interactions with human leucocyte antigen DRB1*15:01 with regard to relapsing-onset and progressive-onset MS. A total of 7520 relapsing-onset cases, 540 progressive-onset cases, and 11,386 controls matched by age, sex, and residential area were included in the analysis.

“Although a vast majority of MS risk alleles are immunological genes, no definite genetic differences have been found between relapsing and progressive onset MS, indicating that the different clinical phenotypes may be opposite ends of the same disease spectrum, rather than different diseases. Our observation is that the DRB1*15:01 allele is comparably distributed in patients with relapsing-onset, and progressive MS is in accordance with these results,” Hedstrom et al wrote.

Environmental factors such as ever smoking was associated with increased risk of both relapsing-onset MS (odds ratio [OR], 1.6 [95% CI, 1.5-1.7]) and progressive-onset MS (OR, 1.9 [95% CI, 1.6-2.3]). Current smoking led to greater impact on disease risk than previous smoking, while cumulative dose of smoking led to significant trends showing increased risk for both MS phenotypes (P values for trend <.00001).

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After subjects provided information regarding current and previous snuff use, researchers concluded that exclusive snuff use was associated with reduced risk of both relapsing-onset MS (OR, 0.7 [95% CI, 0.6-0.9]) and progressive-onset MS (OR, 0.6 [95% CI, 0.4-0.9]).

Information was obtained regarding current heigh and body weight at age 20 years, with body mass index (BMI) calculated by dividing weight in kilograms by heigh in meters squared. All told, being “overweight” was associated with a small increased risk of relapsing-onset MS (OR, 1.3 [95% CI, 1.2-1.4) and progressive-onset MS (OR, 1.2 [95% CI, 0.8-1.6]), whereas obesity had a more pronounced impact on the risk of the disease (relapsing-onset MS: OR, 1.7 [95% CI, 1.4-2.0]; progressive-onset MS: OR, 1.8 [95% CI, 1.0-3.2]).

An increased risk of relapsing-onset MS (OR, 3.0 [95% CI, 2.7-3.3]) and progressive-onset MS (OR, 2.0 [95% CI, 1.6-2.5]) was associated with high EBNA-1 antibody levels, with the risk subsequently increasing as the levels of antibodies increased (P values for trend <.0001).

Hedstrom and colleagues also observed gene-environment interactions in the development of relapsing-onset and progressive-onset MS. Overall, carriers of the DRB1*15:01 allele had an increased risk of developing relapsing-onset MS (OR, 3.5 [95% CI, 3.3-3.8]) and progressive-onset MS (OR, 3.3 [95% CI, 2.6-4.0]).

Aside from snuff use, all of the environmental factors had additive interactions with DRB1*15:01 with regards to both relapsing-onset and progressive-onset MS. These interactions were evaluating by calculating the attributable proportion (AP).

REFERENCE

Hedstrom AK, Hillert J, Olsson T, Alfredsson L. Factors affecting the risk of relapsing-onset and progressive-onset multiple sclerosis. J Neurol Neurosurg Psychiatry. Published online May 13, 2021. doi: 10.1136/jnnp-2020-325688.