Association between sequence variations of the Mediterranean fever gene and the risk of migraine: a case–control study

Abstract

Salih Coşkun,1 Sefer Varol,2 Hasan H Özdemir,2 Sercan Bulut Çelik,3 Metin Balduz,4 Mehmet Akif Camkurt,5 Abdullah Çim,1 Demet Arslan,2 Mehmet Uğur Çevik2 1Department of Medical Genetics, 2Department of Neurology, Faculty of Medicine, Dicle University, Diyarbakir, 3Family Health Center, Batman, 4Department of Neurology, Şanlıurfa Education and Research Hospital, Şanlıurfa, 5Department of Psychiatry, Afsin State Hospital, Kahramanmaraş, Turkey Abstract: Migraine pathogenesis involves a complex interaction between hormones, neurotransmitters, and inflammatory pathways, which also influence the migraine phenotype. The Mediterranean fever gene (MEFV) encodes the pyrin protein. The major role of pyrin appears to be in the regulation of inflammation activity and the processing of the cytokine pro-interleukin-1β, and this cytokine plays a part in migraine pathogenesis. This study included 220 migraine patients and 228 healthy controls. Eight common missense mutations of the MEFV gene, known as M694V, M694I, M680I, V726A, R761H, K695R, P369S, and E148Q, were genotyped using real-time polymerase chain reaction with 5' nuclease assays, which include sequence specific primers, and probes with a reporter dye. When mutations were evaluated separately among the patient and control groups, only the heterozygote E148Q carrier was found to be significantly higher in the control group than in the patient group (P=0.029, odds ratio [95% confidence interval] =0.45 [0.21–0.94]). In addition, the frequency of the homozygote and the compound heterozygote genotype carrier was found to be significantly higher in patients (n=8, 3.6%) than in the control group (n=1, 0.4%) (P=0.016, odds ratio [95% confidence interval] =8.57 [1.06–69.07]). However, there was no statistically significant difference in the allele frequencies of MEFV mutations between the patients and the healthy control group (P=0.964). In conclusion, the results of the present study suggest that biallelic mutations in the MEFV gene could be associated with a risk of migraine in the Turkish population. Moreover, MEFV mutations could be related to increased frequency and short durations of migraine attacks (P=0.043 and P=0.021, respectively). Future studies in larger groups and expression analysis of MEFV are required to clarify the role of the MEFV gene in migraine susceptibility. Keywords: MEFV gene, headache, Familial Mediterranean fever (FMF), biallelic mutations, pyrin (or marenostrin), aura, single nucleotide polymorphisms 

Keywords

• Migraine
• Mediterranean fever gene
• MEFV
• headache
• familial Mediterranean fever
• biallelic mutations.