ABSTRACT
Background & objectives: Fibromyalgia syndrome (FMS) is one of the most common chronic pain conditions of unknown aetiology. Mitochondrial dysfunction has been reported in FMS with some studies reporting the presence of mitochondrial mutation namely A3243G, which also causes mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes. This pilot study was conducted to assess this mutation and also detect large deletions in mitochondrial DNA (mtDNA) in patients with FMS. Methods: Thirty female patients with FMS participated and 30 matched controls were included. Genomic DNA was subjected to polymerase chain reaction (PCR) amplification using specific primers followed by restriction digestion with Apa I enzyme to detect the specific A3243G mtDNA mutation. Long-range PCR was done in two sets to detect the large deletions in the mtDNA. Biochemical parameters including thyroid-stimulating hormone and vitamin D levels were also looked at. Results: None of the patients were found to carry the common mutation or large deletions. Low vitamin D level was a common finding. Hypothyroidism was found in a few patients. Interpretation & conclusions: Although the common mutation or large mtDNA deletions were not detected in blood mtDNA in the FMS patients, mutations in the muscle and sequence variation in mtDNA remained a possibility. Future studies in both blood and muscle tissue including mtDNA sequencing are warranted in such patients to determine if a subset of FMS patients have mitochondrial myopathy.
ABSTRACT
Objective To study the time-and dose-effect of mitochondrial DNA (mtDNA) 4934 bp and 4977 bp deletions in the human peripheral blood irradiated by137 Cs γ-rays,and to evaluate its implication in biological dosimetry.Methods The peripheral blood from five healthy adults was collected and irradiated with γ-rays.The peripheral blood of one healthy adult was irradiated with 5 Gy and cultured for 2,24,48 and 72 h after irradiation.The peripheral blood from the other four healthy adults was cultured for 2 h after 0,0.5,1,2,5 and 10 Gy irradiation.The peripheral blood mtDNA 4934 bp and 4977 bp deletions were detected by real-time polymerase chain reaction and gel electrophoresis.The doseeffect curves were fitted using Curve Expert 1.4 Software.Results mtDNA 4934 bp and 4977 bp deletions were induced at 2 h post-irradiation and the mtDNA 4934 bp deletion had relative high levels at 2 h and 48h after radiation (t =10.782 and 8.966,P ＜ 0.05),and mtDNA 4977 bp deletion reached the highest level at 48 h after radiation (t =7.433,P ＜0.05).mtDNA 4934 bp (t =2.895-8.105,P ＜0.05) and 4977 bp deletion (t =3.006-7.715,P ＜0.05) irradiated at 0.5-10 Gy increased with a dosedependent manner.The incidence of mtDNA 4977 bp deletion was higher than that of 4934 bp deletion for those samples exposed with same dose of irradiation,especially at 10 Gy (t =2.919,P ＜ 0.05),which suggested that 4977 bp deletion might be more sensitive than 4934 bp deletion at high dose.But larger individual differences were found in 4977 bp deletion compared with 4934 bp deletion.The dose-effect equations for 4934 bp deletion and 4977 bp deletion were Y1 =1.178 + 0.1219D (R2 =0.9269) and Y2 =1.2578 +0.1933D (R2 =0.9016),respectively.Conclusions The induction of mtDNA deletion was correlated with radiation dose,and thus it may be a available method for biological dose estimation and prognostic evaluation.