Association between sequence variations of the Mediterranean fever gene and fibromyalgia syndrome in a cohort of Turkish patients

Objective: Fibromyalgia syndrome (FMS) is a common chronic widespread pain syndrome mainly affecting women. Genetic risk factors are known to contribute to the etiology of the syndrome. Clinical features show that FMS and familial Mediterranean fever (FMF) have some overlapping symptoms. Mediterranean fever (MEFV) gene has already been identified as being responsible for FMF. The aim of this study was to explore the frequency and clinical significance of missense mutations and a common polymorphism of MEFV gene in a cohort of Turkish patients with FMS.

Methods: The study included 187 patients with FMS and 190 healthy controls. Genomic DNA was isolated and genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses for the five MEFV gene mutations (M694V, M680I, V726A, E148Q and P369S) and one polymorphism (R202Q).

Results: There were statistically significant differences of the MEFV gene mutation carrier rates and allele frequencies between FMS patients and healthy controls (p=0.002, OR: 2.3, 95% CI: 1.35-4.16 and p=0.003, OR: 2.2, 95% CI: 1.28-3.75, respectively). There was also a significant difference between MEFV mutation carriers and non-carriers with respect to the clinical characteristic of morning fatigue (p=0.045). The genotype and allele frequencies of R202Q polymorphism of MEFV gene showed statistically significant differences between FMS patients and healthy controls (p<0.0001 and p<0.0001, respectively) and especially the homozygous AA genotype was significantly higher in FMS patients than in healthy controls (p=0.0003; OR: 7.43, 95% CI: 2.14-39.75). While 13 of the 44 FMS patients with MEFV mutation had R202Q polymorphism, none of the 22 controls with MEFV mutation had R202Q polymorphism. Stratification analysis according to clinical features for this disease reveals that morning fatigue and irritable bowel syndrome had associations with R202Q polymorphism (p=0.022 and p=0.031 respectively).

Conclusion: The results of this study suggest that MEFV gene mutations and polymorphism are positively associated with predisposition to develop FMS. Further studies with larger populations will be required to confirm these findings.