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Objective: Fibromyalgia Syndrome (FM) is a common disease characterized by generalized body pain, sensitivity in certain physical areas (sensitive points), lowered pain threshold, sleep disorder, fatigue. The study aimed to determine the effects ACE I/D and MTHFR C677T gene polymorphisms in Turkish patients with FM and evaluate if there was an association with clinical features. The etiopathogenesis of FM is still not clearly known. Various viral infections, stress, living conditions, chronic sleep disorders, physical and emotional traumas, major neuro-endocrinal malfunctions as well as genetic factors are considered in the etiopathogenesis of FMS.
Methods: This study included 200 FM patients and 190 healthy controls recruited from the department of Physical Medicine and Rehabilitation at Gaziosmanpasa University in Tokat, Turkey. ACE I/D polymorphism genotypes were determined by using polymerase chain reaction (PCR) by specific primers. The MTHFR C677T mutation was analyzed by PCR-based restriction fragment length polymorphism (RFLP) methods.
Results: We found a statistically significant relation between ACE polymorphism and FM (p0.05, OR: 1.20, 95% CI: 0.82-1.78), but dry eyes, which are among the clinical characteristics of FM, were significantly related with MTHFR C677T mutation (p<0.05).
Conclusion: Angiotensin-converting enzyme is a zinc metallopeptidase involved in blood pressure regulation via angiotensin-renin cascade, generating angiotensin II (ATII) from angiotensin I, and via degradation of the powerful vasodilator bradykinin. Several studies have also demonstrated that ACE might be involved in hypothalamic-pituitary-adrenal axis (HPA) regulation and catecholamine production and is thus required for sympathoadrenal activation during stress. The co-localization of angiotensin with dopaminesynthesizing neurons can suggest an involvement of the brain renin-angiotensin system in regulation of mood. It is suggested that ACE polymorphism is a risk factor for neuropsychiatric disturbances and related diseases. We are thinking that we must investigate the associations between ACE gene I/D polymorphism and FM. Jenkins et al. have also found that in patients with sleep disorders, which are one of the symptoms of fibromyalgia, there were considerable differences in the polymorphism of ACE gene 25-28. These patients were not diagnosed as FM. Since FM is associated with depression and sleep disorders, we investigated the relation of FM and ACE polymorphism. MTHFR mutations also cause cytokine activation. MTHFR is a key enzyme in Hcy metabolism which plays a major role in regulating endothelial function. It regulates Hcy and methionine metabolism and converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate (primary form of folate in circulation). Our findings showed that there are associations of ACE I/D polymorphism with susceptibility of a person for development of fibromyalgia syndrome. Also, an association has been determined between MTHFR C677T polymorphism and dry eyes, which are among the clinical characteristics of FM. Our study is the first report of ACE I/D and MTHFR C677T polymorphisms in fibromyalgia syndrome.