nach oben

Erschienen in:

01.11.2010 | Basic Neurosciences, Genetics and Immunology - Original Article

Genetic TPH2 variants and the susceptibility for migraine: association of a TPH2 haplotype with migraine without aura

verfasst von: Alexander Jung, Andreas Huge, Gregor Kuhlenbäumer, Steffi Kempt, Tanja Seehafer, Stefan Evers, Klaus Berger, Martin Marziniak

Erschienen in: Journal of Neural Transmission | Ausgabe 11/2010

Einloggen, um Zugang zu erhalten

Abstract

The serotonergic system plays a major role in the etiology of migraine. The rate-limiting enzyme in serotonin homeostasis and availability is tryptophan hydroxylase (TPH). The TPH2 isoform is responsible for the cerebral serotonin biosynthesis. To investigate the role of genetic variation in TPH2 in the pathogenesis of migraine eight haplotype tagging SNPs covering the whole TPH2 gene where chosen using Haploview and genotyped in 503 migraineurs and 515 healthy controls. Association analysis was performed on a single SNP and haplotype basis using χ ² and logistic regression analysis. Single SNP analysis revealed a weak association with migraine, which did not remain after correction for multiple testing. Haplotype analyses revealed association of a haplotype with migraine without aura. Stratification by aura and triptan response did not reveal a positive association with the investigated polymorphisms. These results suggest a possible influence of genetic variation in TPH2 in the pathogenesis of migraine.

Abdi H (2007) Bonferroni and Sidak corrections for multiple comparisons. In: Salkind NJ (ed) Encyclopedia of measurement, statistics. Thousand Oaks, Sage

Afridi SK, Giffin NJ, Kaube H, Friston KJ, Ward NS, Frackowiak RS, Goadsby PJ (2005) A positron emission tomographic study in spontaneous migraine. Arch Neurol 62:1270–1275CrossRefPubMed

Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265CrossRefPubMed

Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571PubMed

Bowyer SM, Aurora KS, Moran JE, Tepley N, Welch KM (2001) Magnetoencephalographic fields from patients with spontaneous and induced migraine aura. Ann Neurol 50:582–587CrossRefPubMed

Brandes JL, Saper JR, Diamond M, Couch JR, Lewis DW, Schmitt J, Neto W, Schwabe S, Jacobs D, MIGR-002 Study Group (2004) Topiramate for migraine prevention: a randomized controlled trial. JAMA 291:965–973CrossRefPubMed

Cader ZM, Noble-Topham S, Dyment DA, Cherny SS, Brown JD, Rice GP, Ebers GC (2003) Significant linkage to migraine with aura on chromosome 11q24. Hum Mol Genet 12:2511–2517CrossRefPubMed

Ferrari MD, Saxena PR (1993) On serotonin and migraine: a clinical and pharmacological review. Cephalalgia 13:151–165CrossRefPubMed

Ferrari MD, Odink J, Tapparelli C, van Kempen GM, Pennings EJ, Bruyn GW (1989) Serotonin metabolism in migraine. Neurology 39:1239–1242PubMed

Ferrari MD, Roon KI, Lipton RB, Goadsby PJ (2001) Oral triptans (serotonin 5-HT (1B/1D) agonists) in acute migraine treatment: a meta-analysis of 53 trails. Lancet 358:1668–1675CrossRefPubMed

Gutknecht L, Waider J, Kraft S, Kriegebaum C, Holtmann B, Reif A, Schmitt A, Lesch KP (2008) Deficiency of brain 5-HT synthesis but serotonergic neuron formation in Tph2 knockout mice. J Neural Transm 115:1127–1132CrossRefPubMed

Hadjikhani N, Sanchez del Rio M, Wu O, Schwartz D, Bakker D, Fischl B, Kwong KK, Cutrer FM, Rosen BR, Tootell RB, Sorensen AG, Moskowitz MA (2001) Mechanism of migraine aura revealed by function MRI in human visual cortex. Proc Natl Acad Sci USA 98:4687–4692CrossRefPubMed

Happe S, Vennemann M, Evers S, Berger K (2008) Treatment wish of individuals with known and unknown restless legs syndrome in the community. J Neurol 255:1432–1459CrossRef

Hart BL (1988) Biological basis of the behavior of sick animals. Neurosci Biobehav Rev 12:123–137CrossRefPubMed

Headache Classification Subcommittee of the International Headache Society (2004) The international classification of headache disorders: 2nd edition. Cephalalgia 24(Suppl 1):9–160

Humphrey PP (1991) 5-Hydroxytryptamine and the pathophysiology of migraine. J Neurol 238(Suppl 1):S38–S44CrossRefPubMed

Humphrey PP (2007) The discovery of a new drug class for the acute treatment of migraine. Headache 47(Suppl 1):S10–S19CrossRefPubMed

Lampl C, Bonelli S, Ransmayr G (2004) Efficacy of topiramate in migraine aura prophylaxis: preliminary results of 12 patients. Headache 44:174–176CrossRefPubMed

Launer LJ, Terwindt GM, Ferrari MD (1999) The prevalence and characteristics of migraine in a population based cohort: the GEM study. Neurology 53:537–542PubMed

Lauritzen M (1994) Pathophysiology of the migraine aura. The spreading depression theory. Brain 117:199–210CrossRefPubMed

Loder E (2002) What is the evolutionary advantage of migraine? Cephalalgia 22:624–632CrossRefPubMed

Lucki I (1998) The spectrum of behaviors influenced by serotonin. Biol Psychiatry 44:151–162CrossRefPubMed

Marziniak M, Kienzler C, Kuhlenbäumer G, Sommer C, Mössner R (2009) Functional gene variants of the serotonin-synthesizing enzyme tryptophan hydroxylase 2 in migraine. J Neural Transm 116:815–819CrossRefPubMed

Montagna P (2008) The primary headaches: genetics, epigenetics and a behavioural genetic model. J Headache Pain 9:57–69CrossRefPubMed

Moskowitz MA (2007) Pathophysiology of headache—past and present. Headache 47(Suppl 1):58–63CrossRef

Mulder EJ, Van Baal C, Gaist D, Kallela M, Kaprio J, Svensson DA, Nyholt DR, Martin NG, MacGregor AJ, Cherkas LF, Boomsma DI, Palotie A (2003) Genetic and environmental influences on migraine: a twin study across six countries. Twin Res 6:422–431CrossRefPubMed

Pascual J, Caminero AB, Mateos V, Roig C, Leira R, Garcia-Monco C, Laínez MJ (2004) Preventing disturbing migraine aura with lamotrigine: an open study. Headache 44:1024–1028CrossRefPubMed

Pfaffenrath V, Fendrich K, Vennemann M, Meisinger C, Ladwig K-H, Evers S, Straube A, Hoffmann W, Berger K (2009) Regional variations in the prevalence of migraine and tension-type headache applying the new HIS criteria: the German DMKG Headache Study. Cephalalgia 29:48–57CrossRefPubMed

Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MAR, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a toolset for whole-genome association and population-based linkage analysis. Am J Hum Genet 81:559–575CrossRefPubMed

Richter F, Mikulik O, Ebersberger A, Schaible HG (2005) Noradrenergic agonists and antagonists influence migration of cortical spreading depression in rat—a possible mechanism of migraine prophylaxis and prevention of postischemic neuronal damage. J Cereb Blood Flow Metab 25:1225–1235CrossRefPubMed

Rubino E, Ferrero M, Rainero I, Binello E, Vaula G, Pinessi L (2009) Association of the C677T polymorphism in the MTHFR gene with migraine: a meta-analysis. Cephalalgia 29:818–825CrossRefPubMed

Russell MB, Iselius L, Olesen J (1995) Investigation of inheritance of migraine by complex segregation analysis. Hum Genet 96:726–730CrossRefPubMed

Russell MB, Iselius L, Olesen J (1996) Migraine without aura and migraine with aura are inherited disorders. Cephalalgia 16:305–309CrossRefPubMed

Russell MB, Ulrich V, Gervil M, Olesen J (2002) Migraine without aura and migraine with aura are distinct disorders. A population based twin survey. Headache 42:332–336CrossRefPubMed

Sakowski SA, Geddes TJ, Thomas DM, Levi E, Hatfield JS, Kuhn DM (2006) Differential tissue distribution of tryptophan hydroxylase isoforms 1 and 2 as revealed with monospecific antibodies. Brain Res 1085:11–18CrossRefPubMed

Sanchez del Rio M, Bakker D, Wu O, Agosti R, Mitsikostas DD, Ostergaard L, Wells WA, Rosen BR, Sorensen G, Moskowitz MA, Cutrer FM (1999) Perfusion weighted imaging during migraine: spontaneous visual aura and headache. Cephalalgia 19:701–707CrossRefPubMed

Sicuteri F, Testi A, Anselmi B (1961) Biochemical investigations in headache: increase in hydroxyindoleacetic acid excretion during migraine attacks. Int Arch Allergy Appl Immunol 19:55–58CrossRef

Steiner TJ, Findley LJ, Yuen AW (1997) Lamotrigine versus placebo in the prophylaxis of migraine with and without aura. Cephalalgia 17:109–112CrossRefPubMed

Supornchilpchai W, Sanguarangsirikul S, Maneesri S, Srikiatkhachorn A (2006) Serotonin depletion, cortical spreading depression, and trigeminal nociception. Headache 46:34–39CrossRef

Ulrich V, Russell MB, Ostergaard S, Olesen J (1997) Analysis of 31 families with an apparently autosomal dominant transmission of migraine with aura in the nuclear family. Am J Med Genet 74:395–397CrossRefPubMed

Walther DJ, Bader M (2003) A unique central tryptophan hydroxylase isoform. Biochem Pharmacol 66:1673–1680CrossRefPubMed

Walther DJ, Peter JU, Bashammakh S, Hortnagl H, Voits M, Fink H, Bader M (2003) Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science 299:76CrossRefPubMed

Welch KM (1986) Migraine: a biobehavioural disorder. Cephalalgia 6:103–110PubMed

Wessman M, Kallela M, Kaunisto MA, Marttila P, Sobel E, Hartiala J, Oswell G, Leal SM, Papp JC, Hämäläinen E, Broas P, Joslyn G, Hovatta I, Hiekkalinna T, Kaprio J, Ott J, Cantor RM, Zwart JA, Ilmavirta M, Havanka H, Färkkilä M, Peltonen L, Palotie A (2002) A susceptibility locus for migraine with aura, on chromosome 4q24. Am J Hum Genet 70:652–662CrossRefPubMed

Wolthausen J, Sternberg S, Gerloff C, May A (2009) Are cortical spreading depression and headache in migraine causally linked? Cephalalgia 29:244–249CrossRefPubMed

Zhang X, Beaulieu JM, Sotnikova TD, Gainetdinov RR, Caron MG (2004) Tryptophan hydroxylase-2 controls brain serotonin synthesis. Science 305:217CrossRefPubMed

Zill P, Büttner A, Eisenmenger W, Möller H-J, Ackenheil M, Bondy B (2005) Analysis of tryptophan hydroxylase I and II mRNA expression in the human brain: a post mortem study. J Psychiatr Res 41:168–173CrossRefPubMed

Titel: Genetic TPH2 variants and the susceptibility for migraine: association of a TPH2 haplotype with migraine without aura
verfasst von: Alexander Jung
Andreas Huge
Gregor Kuhlenbäumer
Steffi Kempt
Tanja Seehafer
Stefan Evers
Klaus Berger
Martin Marziniak
Publikationsdatum: 01.11.2010
Verlag: Springer Vienna
Erschienen in: Journal of Neural Transmission / Ausgabe 11/2010
Print ISSN: 0300-9564
Elektronische ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-010-0468-6

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Sozialer Aufstieg verringert Demenzgefahr

24.05.2024 Demenz Nachrichten

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Was nützt die Kraniektomie bei schwerer tiefer Hirnblutung?

17.05.2024 Hirnblutung Nachrichten

Eine Studie zum Nutzen der druckentlastenden Kraniektomie nach schwerer tiefer supratentorieller Hirnblutung deutet einen Nutzen der Operation an. Für überlebende Patienten ist das dennoch nur eine bedingt gute Nachricht.

Thrombektomie auch bei großen Infarkten von Vorteil

16.05.2024 Ischämischer Schlaganfall Nachrichten

Auch ein sehr ausgedehnter ischämischer Schlaganfall scheint an sich kein Grund zu sein, von einer mechanischen Thrombektomie abzusehen. Dafür spricht die LASTE-Studie, an der Patienten und Patientinnen mit einem ASPECTS von maximal 5 beteiligt waren.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 11/2010

Treadmill training restores spatial cognitive deficits and neurochemical alterations in the hippocampus of rats submitted to an intracerebroventricular administration of streptozotocin

Levetiracetam for levodopa-induced dyskinesia in Parkinson’s disease: a randomized, double-blind, placebo-controlled trial

Plasma homovanillic acid correlates inversely with history of childhood trauma in personality disordered and healthy control adults

Facilitation of the development of fungiform taste buds by early intraoral acesulfame-K stimulation to mice

The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis