MEFV Gene Mutation May Make People More Susceptible to Developing AS, Study Indicates

Ashraf Malhas, PhD avatar

by Ashraf Malhas, PhD |

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AS linked to MEFV gene

A meta-analysis of studies on ankylosing spondylitis found a link between a mutation in the Mediterranean fever (MEFV) gene and AS.

AS is a chronic inflammatory disease that is fairly common around the world. Its incidence ranges from 7.4-31.9 per 10,000 people, depending on the region. The main symptoms are back pain and stiffness in the spine.

In some cases, the human leukocyte antigen (HLA)-B27 gene makes people susceptible to AS, but the exact cause of the disease remains unknown. The human leukocyte antigen (HLA) system is a gene complex that encodes cell-surface proteins responsible for regulating the immune system.

Genes are packaged in chromosomes, and researchers have found an association between AS and a region on chromosome 16. The MEFV gene, which is associated with familial Mediterranean fever, is located on the same region of chromosome 16.

Given that 7.5 percent of FMF patients also have AS, researchers have been investigating the association between MEFV gene mutations and AS. But the results of the studies so far have been controversial.

The scientists that did the latest study decided to look again at whether MEFV gene mutations are associated with AS. Their research, “MEFV M694V mutation has a role in susceptibility to ankylosing spondylitis: A meta-analysis,” appeared in the journal PLOSOne,

They reviewed studies about AS through December 31, 2016. The eight articles they chose for their analysis covered 869 AS patients and 879 controls.

They found four MEFV mutations to examine: E148Q, M680I, M694V and V726A. Out of the four, they discovered that only M694V was significantly associated with AS, with 5.06 percent of patients having the mutation, compared with only 1.59 percent of the controls.

MEFV codes for pyrin, a protein involved in an inflammatory pathway that triggers the activation of the inflammatory cytokine interleukin 1 (IL-1). Interestingly, scientists had previously reported an association between certain forms of the gene coding for IL-1 and AS. Taken together, the two observations suggest a link between the IL-1 inflammation pathway and the development of AS.

Researchers acknowledged that their study had several imitations. The patients and controls were mainly from Europe and Asia, which means that the results may not be applicable to other ethnicities. Some of the studies that were analyzed involved small numbers of patients, which could have generated inaccurate statistical results.

The team concluded that “the current meta-analysis established the potential contribution of the MEFV gene mutation, M694V, to the pathogenesis of AS. However, more studies with diverse ethnicities are necessary to validate and extend these conclusions.”