Faculty of Medicine, Department of Medical Biology, Ondokuz Mayis University, Samsun, Turkey.
Clin Chim Acta. 2012 Dec 24;414:36-40. doi: 10.1016/j.cca.2012.07.019. Epub 2012 Aug 7.
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.
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).
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).
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.
纤维肌痛综合征（fibromyalgia syndrome，FMS）是一种常见的慢性广泛性疼痛综合征，主要影响女性。遗传风险因素被认为是该综合征发病的原因。临床特征表明，FMS 和家族性地中海热（familial Mediterranean fever，FMF）有一些重叠的症状。MEFV 基因已被确定为 FMF 的致病基因。本研究的目的是探讨土耳其 FMS 患者中 MEFV 基因突变和常见多态性的频率及其临床意义。
本研究纳入了 187 例 FMS 患者和 190 名健康对照者。使用聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）分析，对 5 种 MEFV 基因突变（M694V、M680I、V726A、E148Q 和 P369S）和 1 种多态性（R202Q）进行基因分型。
FMS 患者与健康对照者的 MEFV 基因突变携带率和等位基因频率存在统计学差异（p=0.002，OR：2.3，95%CI：1.35-4.16 和 p=0.003，OR：2.2，95%CI：1.28-3.75）。MEFV 基因突变携带者与非携带者之间的早晨疲劳的临床特征也存在显著差异（p=0.045）。MEFV 基因 R202Q 多态性的基因型和等位基因频率在 FMS 患者和健康对照者之间存在统计学差异（p<0.0001 和 p<0.0001），尤其是 FMS 患者的纯合 AA 基因型明显高于健康对照组（p=0.0003；OR：7.43，95%CI：2.14-39.75）。在 44 例 FMS 患者中有 13 例存在 MEFV 基因突变，而在 22 例 MEFV 基因突变携带者中没有一例存在 R202Q 多态性。根据疾病的临床特征进行分层分析显示，早晨疲劳和肠易激综合征与 R202Q 多态性有关（p=0.022 和 p=0.031）。
本研究结果提示 MEFV 基因突变和多态性与纤维肌痛综合征的易感性呈正相关。需要更大人群的进一步研究来证实这些发现。
