Study Confirms Link Between Mutations in IL-23A Gene and MS Risk

Malika Ammam, PhD avatar

by Malika Ammam, PhD |

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mutations and disease

A new study confirmed the involvement of three genetic variants, or mutations, of theĀ interleukin-23A (IL-23A) gene, and one variant of its receptor IL-23R, Ā 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, ā€œCharacterization of variations in IL23A and IL23R genes: possible roles in multiple sclerosis and other neuroinflammatory demyelinating diseases,ā€Ā were published in Aging.

Despite the significant advances made in understanding MS and other inflammatory nervous disorders, its causes and molecular mechanisms are still essentially unclear.

A number of studies have shown that complex genetic and environmental factors are involved in the developmental process of inflammatory diseases, where the immune system plays a central role.

Among the involved genes is IL-23A, a gene that coordinates the activity of immune cells when binding to it receptor IL-23R. Several variants of this gene have been linked to autoimmune diseases.

Researchers examined sites of the gene IL-23A and its receptor, IL-23R, in a total of 206 Chinese patients with IDD, including 84 MS patients, and compared the results with those of 300 controls. Serum levels of IL-23A were also compared in different groups of patients with these variants.

ResearchersĀ identified three mutations ā€” rs2066808, rs2371494 and rs11575248 ā€” in theĀ IL-23AĀ gene, and one variant, called rs1884444, in theĀ IL-23R receptor, that are linked to the risk of developing MS or other IDD diseases.

More importantly, the team found clear differences in the serum levels of IL-23A in MS patients, alterations that were mainly caused by the variants in that gene. This observation further supported the involvement of IL-23A in inflammatory nervous disorders.

“The cytokine IL23A has important effects in the differentiation of pro-inflammatory cells, and these cells have been considered to be the main factors in the MS pathogenesis,” the researchers wrote. Their work, by identifying three IL-23A variants that affected serum levels in MS patients, provides “new evidence for the importance of IL-23A and IL-23R in the pathogenesis of the MS disease and demonstrating the differences between MS and other demyelinating syndromes in pathogenesis.”

“As functional genetic variants within the IL-23A gene have significant impacts on the host immune response, they could be excellent candidate targets for genetic association studies,” they concluded.