Additive effects of modifiable risk factors in MS
Multiple sclerosis (MS) is a complex disease in which the risk of onset is influenced by genetic and environmental factors.1 As part of the educational topical symposium on the risk factors of MS at MSVirtual2020, the 8th Joint ACTRIMS-ECTRIMS Meeting held 9–13 September 2020, Professor Anna Hedström (Karolinska Institute, Sweden) provided an overview, covering the additive relationship between genetics and modifiable risk factors for MS.
The influence of smoking on MS risk
Current smokers are more at risk for developing MS compared with other population groups according to Prof. Hedström. Her assessment of several meta-analyses and systematic reviews demonstrated that smoking increases the risk of MS—in some cases up to 50%. One of the reviews highlighted in the presentation found a causal role between smoking and the risk of MS onset.2
SMOKING INCREASES RISK OF MS IN THOSE WITH GENETIC PREDISPOSTIONS
Genetic susceptibility influences the likelihood of MS onset.3 Variations in human leukocyte antigen (HLA) genotypes contribute to the risk of MS disease development.3 Prof. Hedström explained that those with HLA-DRB1*15 positive (+) and those with the HLA-A*02 negative (-) genotypes are both at an increased risk of MS. Her analyses of the MS population in Swedish hospitals and the Swedish MS registry highlighted that smokers with the HLA‑DRB1*15+/HLA-A*02- genotypes experienced a 13-fold risk increase in developing MS, while smokers without the genetic predispositions had a two-fold risk. Similar findings were reproduced in a multinational pooled analysis.1 Her collaboration with Kaiser Permanente Northern California was conducive to findings which indicated that passive smokers experienced increased risks as well, particularly if they were genetically susceptible.
IMMUNE SYSTEM RESPONSES LINKED TO SMOKING
When exploring how smoking potentially leads to the onset of MS, Prof. Hedström stated that immune system responses could be triggered by smoking. She further elaborated that the body’s reactions to smoking, such as local lung inflammation and oxidative stress, can ultimately induce an autoimmune response. Therefore, she encouraged smoking cessation as a possible means to reduce these risks as epigenetic changes that occur with smoking can be reversed by quitting.
Obesity and other risk factors
In addition to smoking, Prof. Hedström’s analyses of the MS population in Sweden also looked at the impact of obesity on MS development. She recommended better management of childhood obesity, as high body mass index (BMI) contributes to low grade chronic inflammation. Although the exact mechanism linking obesity to MS is unclear, it is thought that properties of the adipose tissue present in obese individuals may negatively contribute to MS.4 Prof. Hedström’s findings demonstrated that those with high BMIs and a HLA‑DRB1*15+/HLA-A*02- genetic profile had a greater risk of developing MS than those without the genetic predisposition, similarly to smokers with the same genotypes. Overall, Prof. Hedström’s research demonstrated that smoking and obesity increase the risk of MS onset, however, the risk is even higher in those with the HLA-DRB1*15+/HLA-A*02- genotypes.
There is a need for larger studies
As she concluded her presentation, Prof. Hedström briefly touched on other modifiable lifestyle risk factors. Upon reviewing several studies, she found that shift work, a vitamin D deficiency, alcohol, oral tobacco, and dietary factors also influence the risk of MS development, while the Mediterranean diet and a high fish intake had a protective effect. Prof. Hedström affirmed the need for larger studies in MS populations in order to further understand modifiable lifestyle factors.
People with the genetic susceptibility to the disease may be at a substantially increased risk of developing MS if [they’re] exposed to certain environmental factors
Hedström AK, Katsoulis M, Hössjer O, et al. The interaction between smoking and HLA genes in multiple sclerosis: replication and refinement. European journal of epidemiology 2017;32:909-19.
Degelman ML, Herman KM. Smoking and multiple sclerosis: A systematic review and meta-analysis using the Bradford Hill criteria for causation. Mult Scler Relat Disord 2017;17:207-16.
Hollenbach JA, Oksenberg JR. The immunogenetics of multiple sclerosis: A comprehensive review. J Autoimmun 2015;64:13-25.
Guerrero-García JdJ, Carrera-Quintanar L, López-Roa RI, Márquez-Aguirre AL, Rojas-Mayorquín AE, Ortuño-Sahagún D. Multiple sclerosis and obesity: possible roles of adipokines. Mediators of inflammation 2016;2016.