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© 2009 American Academy of Neurology Mitochondrial DNA haplogroups influence the therapeutic response to riboflavin in migraineursFrom the University Centre for Adaptive Disorders and Headache (C.D., F.P.) and Rehabilitation Unit (C.C.), University of Rome "La Sapienza," Polo Pontino–ICOT, Latina; Headache Clinic (F.P.), IRCCS INM Neuromed, Pozzilli (IS); Department of Neurophysiology of Vision and Neurophthalmology (G.C.), G.B. Bietti Eye Foundation–IRCCS, Rome; Molecular Genetics Laboratory (G.S.G., C.R.), IRCCS "C. Mondino Institute of Neurology" Foundation–IRCCS "San Raffaele," Rome; Molecular Medicine (M.C., F.M.S.), IRCCS "Bambino Gesù," Rome, Italy; Headache Research Unit (D.M., M.B., J.S.), Department of Neurology, Liège University, CHR Citadelle, Liège, Belgium; and IRCCS Neurological Institute "C. Mondino" (M.B.), University Centre for Adaptive Disorders and Headache, Pavia, Italy. Address correspondence and reprint requests to Dr. Cherubino Di Lorenzo, via Franco Faggiana, 34–04100 Latina, Italy cherub{at}inwind.it Objectives: In migraine, an interictal reduction of mitochondrial energy metabolism and a preventive effect of high-dose riboflavin were reported. To explore the relation between the two, we tested if the therapeutic response to riboflavin is associated with specific mitochondrial DNA (mtDNA) haplogroups. We focused our attention on haplogroup H, which is known to differ from others in terms of energy metabolism. Methods: Sixty-four migraineurs completed a 4-month open trial with riboflavin (400 mg QD) and were genotyped blindly for mtDNA haplogroups.
Results: Forty patients responded to riboflavin treatment and 24 were nonresponders. The mtDNA haplogroup H was found in 29 subjects (20 migraine without aura, 9 migraine with aura). Riboflavin responders were more numerous in the non-H group (67.5%). Conversely, nonresponders were mostly H (66.7%). The difference between the two groups was significant ( Conclusions: In this pharmacogenetic study, riboflavin appears to be more effective in patients with migraine with non-H mitochondrial DNA haplotypes. The underlying mechanisms are unknown, but could be related to the association of haplogroup H with increased activity in complex I, which is a major target for riboflavin. Our results may have ethnic implications, since haplogroup H is chiefly found in the European population.
Abbreviations: CI = confidence intervals; MA = migraine with aura; MO = migraine without aura; mtDNA = mitochondrial DNA; OR = odds ratio; OXPHOS = oxidative phosphorylation.
Supplemental data at www.neurology.org. Supported by the EU STREP EUROHEAD (LSHM-CT-2004-5044837) (Workpackage 9) and by research grant 3.4.563.04 of the National Fund for Scientific Research-Belgium to J.S. Disclosure: The authors report no disclosures. Medication: Riboflavin (Riboflavinum D 2914A; Federa, Brussels). Received October 17, 2008. Accepted in final form February 9, 2009. This article has been cited by other articles:
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2 = 7.07; p = 0.01). The presence of aura had no influence on riboflavin's effectiveness (
