Abstract
Chronic migraine (CM) prevalence ranges around 1–5%. Most of these patients usually treat their acute attacks with triptans, whose efficacy is extremely variable. A genetic basis for migraine is evident and many susceptibility genes have been described, as well as gene polymorphisms possibly implied in therapy response. Several factors could be involved in the evolution of episodic migraine into a chronic form, such as natural history, psychiatric comorbidity, and the individual’s response to therapy. During a study aimed at detecting connections between genotype and response to triptans administration, we characterized a CM population for polymorphisms in the genes coding for monoamine oxidase A, g-protein beta 3 and the cytochromes CYP3A4 and CYP1A2. Alleles and genotypes distributions were compared with known frequencies of healthy Caucasian populations. A significant association with CM was found for the long allele of monoamine oxidase A 30 bp VNTR and CYP1A2*1F variant. Such genomic analysis is part of an integrated platform able to evaluate different levels of metabolic pathways of drugs in CM and their influence in the chronicization process.
Keywords: Chronic migraine, Triptans, Pyrosequencing, Pharmacogenomics, Genetic liability
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Conflict of interest
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References
- 1.Headache Classification Committee. Olesen J, M-G- Bousser, Diener HC, Dodick D, First M, Goadsby PJ, Göbel H, Lainez MJA, Lance JW, Lipton RB, Nappi G, Sakai F, Schoenen J, Silberstein SD, Steiner TJ. New appendix criteria open for a broader concept of chronic migraine. Cephalalgia. 2006;26:742–746. doi: 10.1111/j.1468-2982.2006.01172.x. [DOI] [PubMed] [Google Scholar]
- 2.Manack A, Turkel C, Silberstein S. The evolution of chronic migraine: classification and nomenclature. Headache. 2009;49:1206–1213. doi: 10.1111/j.1526-4610.2009.01432.x. [DOI] [PubMed] [Google Scholar]
- 3.Natoli JL, Manack A, Dean B, Butler Q, Turkel CC, Stovner L, Lipton RB (2009) Global prevalence of chronic migraine: a systematic review. Cephalalagia. doi:10.1111/j.1468-2982.2009.01941.x [DOI] [PubMed]
- 4.Ferrari A, Sternieri E, Ferraris E, Bertolini A. Emerging problems in the pharmacology of migraine: interactions between triptans and drugs for prophylaxis. Pharmacol Res. 2003;48:1–9. [PubMed] [Google Scholar]
- 5.Schürks M, Kurth T, Stude P, Rimmbach C, Jesus J, Jonjic M, Diener HC, Rosskopf D. G protein beta3 polymorphism and triptan response in cluster headache. Clin Pharmacol Ther. 2007;82:396–401. doi: 10.1038/sj.clpt.6100159. [DOI] [PubMed] [Google Scholar]
- 6.Deckert J, Catalano M, Syagailo YV, Bosi M, Okladnova O, Di Bella D, Nöthen MM, Maffei P, Franke P, Fritze J, Maier W, Propping P, Beckmann H, Bellodi L, Lesch KP. Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder. Hum Mol Genet. 1999;8:621–624. doi: 10.1093/hmg/8.4.621. [DOI] [PubMed] [Google Scholar]
- 7.Rodriguez S, Gaunt TR, Day INM (2009) Hardy–Weinberg equilibrium testing of biological ascertainment for Mendelian randomization studies. Am J Epidemiol. doi:10.1093/aje/kwn359 [DOI] [PMC free article] [PubMed]
- 8.Thibaudin L, Berthoux P, Thibaudin D, Mariat C, Berthoux F. G protein beta3 subunit C825T polymorphism in primary IgA nephropathy. Kidney Int. 2004;66:322–328. doi: 10.1111/j.1523-1755.2004.00734.x. [DOI] [PubMed] [Google Scholar]
- 9.Garsa AA, McLeod HL, Marsh S (2005) CYP3A4 and CYP3A5 genotyping by Pyrosequencing. BMC Med Genet 9;6:19 [DOI] [PMC free article] [PubMed]
- 10.Pavanello S, Pulliero A, Lupi S, Gregorio P, Clonfero E. Influence of the genetic polymorphism in the 5′-noncoding region of the CYP1A2 gene on CYP1A2 phenotype and urinary mutagenicity in smokers. Mutat Res. 2005;587:59–66. doi: 10.1016/j.mrgentox.2005.08.008. [DOI] [PubMed] [Google Scholar]
- 11.Filic V, Vladic A, Stefulj J, Cicin-Sain L, Balija M, Sucic Z, Jernej B. Monoamine oxidases A and B gene polymorphisms in migraine patients. J Neurol Sci. 2005;228:149–153. doi: 10.1016/j.jns.2004.11.045. [DOI] [PubMed] [Google Scholar]
- 12.Sabol SZ, Hu S, Hamer D. A functional polymorphism in the monoamine oxidase A gene promoter. Hum Genet. 1998;103:273–279. doi: 10.1007/s004390050816. [DOI] [PubMed] [Google Scholar]
- 13.Panconesi A. Serotonin and migraine: a reconsideration of the central theory. J Headache Pain. 2008;9:267–276. doi: 10.1007/s10194-008-0058-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Sachse C, Brockmoller J, Bauer S, Roots I. Functional significance of a C→A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol. 1999;47:445–449. doi: 10.1046/j.1365-2125.1999.00898.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Nakajima M, Yokoi T, Mizutani T, Kinoshita M, Funayama M, Kamataki T. Genetic polymorphism in the 5’-flanking region of human CYP1A2 gene: effect on the CYP1A2 inducibility in humans. J Biochem Tokyo. 1999;125:803–808. doi: 10.1093/oxfordjournals.jbchem.a022352. [DOI] [PubMed] [Google Scholar]
- 16.Goodman MT, McDuffie K, Kolonel LN, Terada K, Donlon TA, Wilkens LR, Guo C, Le Marchand L. Case–control study of ovarian cancer and polymorphisms in genes involved in catecholestrogen formation and metabolism. Cancer Epidemiol Biomarkers Prev. 2001;10:209–216. [PubMed] [Google Scholar]
- 17.Cornelis MC, El-Sohemy A, Campos H. Genetic polymorphism of CYP1A2 increases the risk of myocardial infarction. J Med Genet. 2004;41:758–762. doi: 10.1136/jmg.2004.022012. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Basile VS, Ozdemir V, Masellis M, Walker ML, Meltzer HY, Lieberman JA, Potkin SG, Alva G, Kalow W, Macciardi FM, Kennedy JL. A functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene: association with tardive dyskinesia in schizophrenia. Mol Psychiatry. 2000;5:410–417. doi: 10.1038/sj.mp.4000736. [DOI] [PubMed] [Google Scholar]
- 19.Rapoport AM, Tepper SJ, Sheftell FD, Kung E, Bigal ME. Which triptan for which patient? Neurol Sci. 2006;27(Suppl 2):S123–S129. doi: 10.1007/s10072-006-0586-y. [DOI] [PubMed] [Google Scholar]
- 20.Skarke C, Kirchhof A, Geisslinger G, Lötsch J. Rapid genotyping for relevant CYP1A2 alleles by pyrosequencing. Eur J Clin Pharmacol. 2005;61:887–892. doi: 10.1007/s00228-005-0029-3. [DOI] [PubMed] [Google Scholar]
- 21.Simmaco M, Borro M, Missori S, Martelletti P. Pharmacogenomics in migraine: catching biomarkers for a predictable disease control. Expert Rev Neurother. 2009;9:1267–1269. doi: 10.1586/ern.09.80. [DOI] [PubMed] [Google Scholar]
- 22.Asuni C, Cherchi A, Congiu D, Piccardi MP, Del Zompo M, Stochino ME. Association study between clinical response to rizatriptan and some candidate genes. J Headache Pain. 2007;8:185–189. doi: 10.1007/s10194-007-0388-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Farinelli I, Filippis S, Coloprisco G, Missori S, Martelletti P. Future drugs for migraine. Inter Emerg Med. 2009;4:367–373. doi: 10.1007/s11739-009-0273-0. [DOI] [PubMed] [Google Scholar]
- 24.Stovner L, Tronvik E, Hagen K. New drugs for migraine. J Headache Pain. 2009;10:395–406. doi: 10.1007/s10194-009-0156-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
