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Genetic Factors in Multiple Sclerosis

Posted on April 19, 2021
Medically reviewed by
Evelyn O. Berman, M.D.
Article written by
Amanda Agazio, Ph.D.

Although scientists do not fully understand what causes multiple sclerosis (MS), they believe that genetic and environmental factors play a role in the condition’s development. In fact, some research has found that genetics contribute to 54 percent of the risk factors associated with MS. The remaining risk is likely due to environmental factors.

MS is an autoimmune disease characterized by the destruction of the protective myelin sheath that covers nerve cells in the central nervous system. The autoimmune attacks lead to lesions in the brain, spinal cord, and optic nerves, making it difficult for nerve cells to function properly.

Though the specific causes of MS are still unknown, science has come a long way. With the advent of the technology for genome-wide association studies (GWAS), scientists have been able to associate the expression of certain genes and the risk of developing MS.

What Genes Are Associated With MS?

Multiple GWAS studies have identified more than 110 genes associated with the risk of MS. Some genes are more relevant than others and are associated with a higher risk factor for the development of the condition.

HLA-DRB1

A version of the HLA-DRB1 gene known as HLA-DRB1*15:01 is perhaps the most relevant gene connected to MS. A person with the HLA-DRB1*15:01 gene is three times as likely to develop MS as someone without the gene.

HLA-DRB1 is one of several human leukocyte antigens (HLAs). HLA genes enable T cells (a type of white blood cell in the immune system) to identify small proteins on the surface of an invading or harmful cell so they can either kill that cell or recruit other cells from the immune system to attack.

The HLA genes are diverse, and there are many different versions of each gene, called alleles. Scientists have yet to understand why the expression of the HLA-DRB1*15:01 allele is associated with a greater risk for MS. However, MS is an autoimmune disease and HLA-DRB1*15:01 is important for the activation of immune cells. It may be that this gene has something to do with the activation of immune cells against the central nervous system.

L7R Alpha and IL2R Alpha

Other genes related to MS susceptibility are also associated with the immune system. These include the IL7R alpha and IL2R alpha genes. (The IL in both names stand for “interleukin.”)

Both of these genes help make receptors for cytokines — the inflammatory mediators of the immune system — on the cell surface. Scientists have identified genetic changes — called single nucleotide polymorphisms (or SNPs) — within the IL7R alpha and IL2R alpha genes. These changes affect the way these receptors work. Someone carrying these SNPs on their genes for IL7R alpha and IL2R alpha has a 1.5 times higher chance of developing MS.

Is MS Hereditary?

Although there are some genetic associations with MS, the disease itself is not technically hereditary. Hereditary diseases get passed down among family members with a particular pattern, but MS doesn’t show a predictable pattern among families.

However, MS still has some genetic components. Blood relatives may have a higher risk of developing MS when a family member has it. For example, a sibling or child of someone with MS may have up to a 4 percent chance of developing MS — a 10- to 20-fold increase in risk compared to the general population. The identical twin of someone with MS is at even higher risk, with a 30 percent chance of developing the disease. Because identical twins share all genetic material, the fact that a twin’s risk is not 100 percent affirms that factors other than genetics play a role in MS.

Read more about the heredity of MS.

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Evelyn O. Berman, M.D. is a neurology and pediatric specialist and treats disorders of the brain in children. Review provided by VeriMed Healthcare Network. Learn more about her here.
Amanda Agazio, Ph.D. completed her doctorate in immunology at the University of Colorado Anschutz Medical Campus. Her studies focused on the antibody response and autoimmunity. Learn more about her here.

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