genetic variants

Genetic variants in genes mostly active in the brain and spinal cord — the central nervous system — are associated with the severity of multiple sclerosis (MS), and linked to a faster accrual of disability and greater signs of brain tissue damage, a new study found. Importantly, researchers estimated…

People with a higher genetic risk for multiple sclerosis (MS) are significantly more likely to develop the disease at an earlier age, a large study found. Specifically, those with the highest genetic risk were on average five years younger at the time their symptoms started than those with the…

Genetic variants may contribute to increased levels of antibodies against proteins of the Epstein-Barr virus — a known environmental risk factor for multiple sclerosis (MS) — in MS patients and their siblings, a study suggests. The study, “EBNA-1 titer gradient in families with multiple sclerosis indicates a…

A high genetic risk for multiple sclerosis (MS) is associated with structural alterations in white matter — brain regions composed mainly of nerve fibers — in childhood, findings from a large study show. Brain volume, however, was not affected by genetic risk in the more than 2,000 children whose…

The small variants seen in the DNA code among individuals may affect the ability of oligodendrocytes to produce myelin, the protective coat surrounding neurons and whose destruction is a hallmark of multiple sclerosis (MS), a study reported. These findings open the possibility of new therapeutic options that target the…

A new large-scale genetic map implicates broad immune system dysfunction in patients with multiple sclerosis (MS), suggests a key role of brain immune cells called microglia, and indicates an MS-related gene variant located in the X chromosome. Altogether, the findings — the result of the largest reported study…

A specific type of immune cell in a particular activation state is linked to such immune diseases as multiple sclerosis (MS) and inflammatory bowel disease (IBD), a collaborative research study found. Disease-associated genetic variants — changes in DNA sequences or mutations in genes — can affect the response of immune…

Genetic variants that enhance the activity of the NLRP3 inflammasome or the interleukin-1 beta cytokine are linked to higher severity and progression of multiple sclerosis, a study suggests. Previous studies with mouse models of MS have shown that a complex of innate immune system receptors and sensors, known as the inflammasome, is likely a player promoting the immune system’s attack on the central nervous system in MS and, consequently, the loss of myelin. Follow-up studies showed that people carrying mutations that enhance the function of the NLRP3 inflammasome — one of the three components of the inflammasome complex — had a worse prognosis, once again supporting the role of the inflammasome in MS. Once activated, the inflammasome triggers an enzyme called caspase-1 that promotes the production of two very powerful proinflammatory cytokines called interleukin (IL)-1 beta and IL-18. To further evaluate the role of the inflammasome in MS, a team led by researchers at the Universidade de Sao Paulo in Brazil analyzed the genetic sequence of five inflammasome genes — NLRP1, NLRP3, NLRC4, IL-1 beta, and IL-18 — in blood samples retrieved from 264 patients diagnosed with MS or other demyelinating diseases. They also analyzed 233 healthy individuals used as controls. The team specifically looked at eight variations in certain nucleotides (the building blocks of DNA), called single nucleotide polymorphisms (SNPs). Previous studies reported a link between SNPs in inflammasome-related genes and certain forms of MS. Results showed that SNPs associated with low serum levels of IL-18 were significantly less frequent in MS patients than in controls. In contrast, variants that enhance the function of NLRP3 and IL-1 beta were associated with severity and progression of MS, as measured by the Expanded Disability Status Scale. These results suggest that the "activation of NLRP3 inflammasome could represent a risk factor for MS clinical presentation,” the researchers wrote. A particular variant in the NLRC4 gene was less frequent in patients whose disease progressed rapidly compared with those who had a slower disease, an intriguing observation, according to researchers, suggestive of a “protection effect of this variant against a bad prognosis.” Carriers of this variant also responded better to treatment with interferon-beta. Regarding MS type, the genetic variant that promotes the function of the IL-1 beta gene was significantly more frequent in progressive forms of MS than in relapsing-remitting MS, strengthening once again the negative effects of IL-1 beta in the disease. An analysis of inflammasome activity in blood monocytes, a group of immune cells, showed that the inflammasome is permanently activated in MS compared with healthy controls. "This study emphasizes that a constitutive activation of NLRP3 inflammasome, principally through IL-1 beta production, represents a risk factor for both the development of MS and the progression to severe forms of the disease. On the other hand, low IL-18 production and/or NLRC4 activation were beneficial for MS patients,” the team concluded.

Genetic variants in the CPXM2, IGSF9B, and NLRP9 genes were found to potentially shape the disease course of multiple sclerosis (MS), and may be used as biomarkers to identify those with an aggressive or…

Researchers have found a link between variations in two genes that control our 24-hour biological clock and the risk of a person developing multiple sclerosis. The study, “Association of circadian rhythm genes ARNTL/BMAL1 and CLOCK with multiple sclerosis,” was published in the journal PLOS ONE. Scientists know MS…

A new study confirmed the involvement of three genetic variants, or mutations, of the interleukin-23A (IL-23A) gene, and one variant of its receptor IL-23R,  in the risk of developing multiple sclerosis (MS) and other related inflammatory nervous disorders, together known as inflammatory demyelinating diseases (IDD). Details of this study, “Characterization of…

A variant in the TYK2 gene, which encodes an immune system protein, may work to protect people from autoimmune disorders, including multiple sclerosis (MS), without overly depressing the body’s ability to fight opportunistic infections, researchers at the University of Oxford report. Their study, “Resolving TYK2 Locus Genotype-To-Phenotype Differences In Autoimmunity,” was published…

A genome-wide analysis of over 110,000 people allowed researchers with the International Multiple Sclerosis Genetics Consortium (IMSGC) to discover 200 genetic loci (the position of genes on a chromosome) that are common to people with multiple sclerosis (MS). The findings were given in the presentation, “200 loci complete the genetic puzzle of multiple sclerosis,” by Dr. Nikolaos…

Obese children and young adults appear to be at a considerably higher risk of developing multiple sclerosis (MS), according to researchers at the McGill University in Canada and collaborators at the University of Bristol in the U.K., who found a causal relationship between the two. Their study, “…

Regions of DNA called super-enhancers regulate immune cell activity, including the body’s response to threats like inflammation or pathogens, and now scientists have found that they also harbor genetic variants associated with autoimmune diseases — gene variants that may be the “master switches” for these conditions. The findings were described in the study “…

An Open Access research article published in the journal BMC Medical Genetics notes that multiple sclerosis (MS) has a strong genetic component, observing high MS prevalence in European populations including those of Ashkenazi Jewish origin, and low in African and Asian populations also including those of…

Personalized medicine, often applied to treat cancer, may be possible for patients with multiple sclerosis as well. Certain patients respond differently to certain multiple sclerosis medications, such as interferon-β (IFNβ), and researchers at San Raffaele Scientific Institute in Milan may have an answer as to why. The team, led by…

In a recent meta-analysis published in the International Journal of Molecular Sciences, a team of researchers found evidence regarding the association between specific polymorphisms of the gene CD24 and MS using a method that combined data from case-control studies with family-based data. Multiple sclerosis (MS) is a chronic and…

Dr. Jose Álvarez-Cermeño and Dr. Luisa Villar from Instituto Ramón y Cajal de Investigación Sanitaria in Madrid, Spain recently published in the journal Nature Reviews Neurology a review on the work developed by Dr. An Goris and colleagues on the link between genetic factors and multiple sclerosis…