Two newly identified MEFV gene variants may be associated with generalized pustular psoriasis (GPP), according to research in the Journal of the American Academy of Dermatology.
Until now, researchers have reported six genes associated with GPP. Although these genes are widely used for diagnosis and treatment, there are GPP patients who do not have any variants of these genes.
Researchers at Nagoya University Graduate School of Medicine in Japan used next-generation sequencing to investigate the genes of Japanese patients with GPP. They found that higher frequencies of two MEFV gene variants, p.Arg202Gln and p.Ser503Cys, were associated with GPP. In particular, 21% of the patients carried the variant p.Arg202Gln variant and 13% carried the p.Ser503Cys variant.
Pyrin, the product of MEFV, regulates inflammatory pathways, but specific variants of pyrin induce excessive neutrophil migration to tissues, eventually triggering excessive inflammation. This finding suggests a likely path for the disease.
Therapies targeting inflammatory pathways related to MEFV may be a promising therapeutic strategy for patients with these variants. “There is the possibility of repurposing therapeutic medications for familial Mediterranean fever, such as colchicine which inhibits pyrin inflammasome formation as treatment options for MEFV-variant-associated GPP, although anti-IL-1 therapy has been tried in GPP with limited success,” the researchers conclude.
