Multiple sclerosis is an autoimmune disease that damages the nerves in the brain and spinal cord. It attacks around 400K people in the US with constantly increasing rates. In addition to environmental factors, different genes may play a role in this complex condition. Read on to learn the facts about MS prevalence, genetic factors, and potential ways to lower the risk.
Prevalence and Epidemiology
The popular epidemiological notion is that MS frequency increases with geographic latitudes .
According to the Atlas: Multiple Sclerosis Resources in the World 2008 published by the World Health Organization (WHO), the global median estimated prevalence for multiple sclerosis is 30 per 100,000 individuals .
The incidence of multiple sclerosis is low in childhood but drastically increases after 18 years of age, peaking around 25 to 35 years and declining after .
In 2015, about 18,500 individuals died from multiple sclerosis .
Despite these numbers, multiple sclerosis only marginally reduces the life expectancy of an individual but greatly diminishes the quality of life .
Multiple Sclerosis Genes
It’s important to note that just because certain genotypes are associated with a condition or irregular lab marker, it doesn’t necessarily mean that everyone with that genotype will actually develop the condition. Many different factors, including other genetic and environmental factors, can influence the risk of multiple sclerosis.
Different ethnic populations around the world have different prevalence and susceptibility to multiple sclerosis that cannot be explained by environmental factors alone .
Individuals with relatives affected by multiple sclerosis have a higher probability of developing the disease .
Identical twins have a 30% chance of both developing MS if one of them develops it. First-degree relatives of individuals affected by multiple sclerosis are 10 – 25 times more likely to develop the disease than the general population [9, 10].
Genetic variations may play a role in multiple sclerosis. Several genetic regions have been implicated in the development of the disease. The most prevailing genes are the HLA genes which are contained in the major histocompatibility complex .
Despite the complexity and diversity of those genes, recent advances in genotyping have led to the discovery of at least 16 more genes (other than HLA) associated with susceptibility to multiple sclerosis .
Genome-wide association studies have found 52 risk alleles associated with the development of multiple sclerosis (HLA-DRb1 gene is the strongest correlation) .
Genes involved with Multiple Sclerosis:
The following are the genes associated with Multiple Sclerosis. Some genes are more problematic than others with regard to the risk factor.
- HLA-DRB1*1501 – rs3135388 A allele: This gene is the strongest genetic factor tied to multiple sclerosis. This gene is involved in the recognition of foreign material and pathogens by the immune system [14, 15].
- IL2RA – rs2104286 T allele: This gene is associated directly with the initiation of inflammation in the brain, which has a link with MS severity . This gene demonstrates that there is a significant difference between the sporadic and familial components of the disease .
- IL7R – rs6897932 allele: This gene is associated with patients who have developed progressive MS, so it may be a factor for the course of the disease .
- CLEC16A gene2: This gene is excessively expressed in multiple sclerosis patients. It also has been described as a controller for the previously mentioned HLA class II producing gene in a large genetic pathway [18, 19].
- CD226 gene3: This gene is associated with some severe cases of multiple sclerosis. It is essential in the activation of the regulatory T cells .
- CYP27B1 gene: This gene contributes to vitamin D deficiency, which has a direct association with MS .
- SOCS1 gene: This gene suppresses the autoimmune responses (cytokines)of the human body, and an absence of the gene leads directly to inflammation. This is because SOCS1 is a key regulator of cytokine transmission and is correlated with both the CLEC16A gene and the DEXI gene [22, 23].
- RGS1 – rs2760524 allele: This gene shows both an association with multiple sclerosis as well as Celiac Disease. It encodes a molecule (G-protein signaling molecule) that is in charge of protein signaling in the development of the immune system .
- IL12A – rs4680534 allele: This gene forms an IL-12 cytokine that ameliorates the immune system through its role in T helper production .
- MPHOSPH9/CDK2API – rs1790100 allele: There is not much information for the MPHOSPH9 gene; however, the CDK2API does affect the level of RNA production. Specifically, this gene is an S-phase growth suppressor. A lower production of this gene is associated with the increased susceptibility of MS .
- PTGER4 – rs4613763 allele: This gene is down-regulated in some MS patients cells and is involved with anti-inflammation .
- OLIG3/TNFAIP3 – rs9321619 allele: The OLIG gene is a significant factor of the nervous system development. The impairment of Olig3 may correlate with MS .
- ZMIZ1 – rs1250540 allele: This gene is decreased in autoimmunity responses. In MS specifically, this protein has reduced production, which can be caused by Epstein Barr Virus and vitamin D deficiency .
- CXCR4 – rs882300 allele: This gene can be found directly on inflammatory lesions in multiple sclerosis patients. It plays a significant part in a chemokine/receptor pair throughout the process of central nervous system inflammation .
Multiple Sclerosis Prevention
Multiple sclerosis is a complex disease with many contributing factors that are not fully understood. There isn’t a known way to prevent MS, but some environmental risk factors can be controlled. Despite the promising preliminary research, more studies are needed before drawing conclusions.
Higher vitamin D blood levels may be protective against developing multiple sclerosis (MS), according to some researchers. In one study on women, each 10 nmol/L increase in blood vitamin levels was associated with a 20% decreased the risk of multiple sclerosis [30, 31, 32].
Also, higher vitamin D levels were associated with a reduced worsening and recurrence of multiple sclerosis symptoms. In a study, each 10 nmol/l increase resulted in up to a 12% reduction in recurrence [33, 34].
According to another study, optimal blood concentrations of this vitamin may reduce disease-related complications (including increased bone degradation, fractures, and muscle weakness) .
Additional large-scale studies are needed to confirm these findings.
One group of researchers found that increased sun exposure during ages 6 – 15 years was associated with a decreased risk of multiple sclerosis. Similarly, outdoor activities were associated with a reduced multiple sclerosis risk [36, 37].
These two factors are mainly responsible for much higher MS rates on higher latitudes .
Therefore, smoking cessation is a crucial step towards lowering the MS risk.
- Multiple Sclerosis: Causes, Symptoms, Diagnosis, and Risk Factors
- Multiple Sclerosis: Diets and Complementary Approaches