Ministry of Health Mental Health Center, Anxiety and Stress Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Clin Exp Rheumatol. 2009 Sep-Oct;27(5 Suppl 56):S51-6.
Fibromyalgia syndrome (FM) is an idiopathic chronic pain syndrome characterised by widespread nonarticular musculoskeletal pain, generalised tender points, in the absence of inflammatory or structural musculoskeletal abnormalities, accompanied by a constellation of symptoms that include fatigue and disturbances of sleep and mood. Catechol-O-methyltransferase (COMT) is the major catecholamine-clearing pathway and involved in the mediation of pain perception in humans, and the hypothesized role of pain perception in FM. The association between Val/Met polymorphism at the COMT gene was evaluated in FM disorder.
209 FM female patients were compared with 152 of their non-affected relatives. DNA was obtained from all family members and extracted. We used the logistic based variant of the transmission disequilibrium test to assess association (and linkage) without confounding effect of population stratification.
We observed an association between FM and the COMT val(158) met polymorphism in a dose response effect of the COMT genotype and the number of pressure points reported. We also observed that non-affected relatives of FM patients had a reduced percentage of the COMT met allele.
Our results are consistent with carriers of the COMT met/met genotype showing increased sensitivity to pain as one mechanism for the role of this gene in conferring risk for FM. We suggest that the reduced frequency of the met allele in the non-affected relatives acts as a 'protective' allele in this group and prevents the development of clinical FM.
纤维肌痛综合征(FM)是一种特发性慢性疼痛综合征,其特征为广泛的非关节肌肉骨骼疼痛、全身性压痛点,不存在炎症或结构性肌肉骨骼异常,并伴有一系列症状,包括疲劳、睡眠和情绪紊乱。儿茶酚-O-甲基转移酶(COMT)是主要的儿茶酚胺清除途径,参与人类疼痛感知的调节,以及疼痛感知在 FM 中的假设作用。在 FM 障碍中评估了 COMT 基因 Val/Met 多态性的关联。
将 209 名 FM 女性患者与 152 名无该病的亲属进行比较。从所有家庭成员中获取并提取 DNA。我们使用基于逻辑的传递不平衡检验变体来评估关联(和连锁),而不受群体分层的混杂影响。
我们观察到 FM 与 COMT val(158)met 多态性之间存在关联,这种关联与 COMT 基因型和报告的压痛点数呈剂量反应效应。我们还观察到 FM 患者的无病亲属携带 COMT met 等位基因的百分比降低。
我们的结果与 COMT met/met 基因型携带者对疼痛的敏感性增加一致,这是该基因在赋予 FM 风险中的作用的一种机制。我们认为,无病亲属中 met 等位基因的频率降低在该组中起到了“保护”作用,防止了临床 FM 的发展。