Understanding the Role of Genes and Environmental Factors in Multiple Sclerosis Progression: A Breakthrough Study

2023-07-14 14:01:07

More than 200 “MS genes” are now known. Genes alone are not enough to trigger MS. According to the current state of science, so-called environmental factors are also needed: circumstances and influences that come later in life, such as certain viruses or insufficient exposure to the sun.

A team from Cambridge and San Francisco has now discovered a gene variant that promotes the progression of the disease. Carriers of this variant have a higher risk of losing their ability to walk, for example. A kind of genetic gas pedal, which absurdly accelerates the loss of mobility.

Prophylactic drugs but no prognosis

MS is not just MS. There are people with very mild, benign courses who experience hardly any limitations and disabilities from MS throughout their lives. And there are those in whom the disease progresses very rapidly. These extremes are comparatively rare. However, the majority of patients are found somewhere between these two poles. Many cope well with their limitations, lead an active life despite MS, some retire early, others have problems coping with everyday life despite retirement. You just don’t know in advance which group you belong to. How MS will develop throughout life. MS cannot yet be cured, nor can the individual course of a patient be predicted.

However, in order to treat appropriately, i.e. to be able to choose the right immunomodulatory drug for one’s own course without over- or under-treating, methods would be important to determine the severity of one’s own course, and in advance. Because the active ingredients used today have a prophylactic effect, so they can slow down MS, but rarely restore lost abilities.

More dependent on walking aids

This is exactly what the current find could contribute to. However, according to the authors of the study, it still has to be tested in even larger gene pools. The “progression gene” is located on chromosome 2. People with MS who have this gene variant on both chromosomes 2 are dependent on a walking aid on average 3.7 years earlier than people without this gene variant.

This is what the researchers led by Stephen Sawcer and Sergio Baranzini found out. To do this, they searched for course-modifying gene variants in a new genome-wide association study. They examined the genome of 22,000 MS patients using a chip at millions of locations and compared their progression. And got a hit: It is SNP (Single Nucleoid Polymorphism) rs 10191329.

Gene variant and endogenous viruses

It is striking that the gene variant rs10911329, in contrast to the gene variants found so far, is not in genes that are linked to the immune system. For this, it is located in the vicinity of the genes DYSF and ZNF683. And these genes, in turn, are active in the brain and spinal cord.

The first gene has to do with repairing damaged cells, the second probably helps keep endogenous viral infections at bay. This made the research team sit up and take notice, because in addition to the exogenous Epstein-Barr virus, the endogenous retrovirus type W41 is also suspected of triggering MS.

A second suspicious gene variant (rs 149097173) also produced a difference, but this was not significant at 3.3 years.

Vitamin D deficiency, obesity, smoking and level of education

The research team also examined genetic connections to suspected characteristics. Both vitamin D deficiency and obesity are associated with the risk of severe disease, statistically speaking. And there are gene variants that promote vitamin D deficiency and obesity. However, according to Mendelian randomization (which checks a possible causal relationship), the gene variants were not decisive for severe courses. According to the current state of knowledge, vitamin D deficiency and obesity appear to be acquired factors (i.e. after conception or often only after birth).

Not smoking and a higher level of education, both acquired factors, seem to give people with MS more resilience: they lived longer without a walking aid on average than smokers and/or people with MS with a lower level of education.

It should be noted that the significant results from the study only show average values ​​and tendencies. Not every MS patient with the corresponding gene variant, not every smoker or obese patient automatically has an unfavorable course of MS. You can’t change anything about the genes anyway, except to adjust your treatment accordingly. Smoking and obesity could of course be changed and would benefit everyone, not just in relation to MS.

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