title: Genetic TPH2 variants and the susceptibility for migraine: association of a TPH2 haplotype with migraine without aura.
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 χ² 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.
authors.affiliation: Department of Neurology, University Hospital of Muenster, University of Muenster, Albert-Schweitzer-Strasse 33, 48149 Münster, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Jung
authors.forename: Andreas
authors.initials: A
authors.lastname: Huge
authors.forename: Gregor
authors.initials: G
authors.lastname: Kuhlenbäumer
authors.forename: Steffi
authors.initials: S
authors.lastname: Kempt
authors.forename: Tanja
authors.initials: T
authors.lastname: Seehafer
authors.forename: Stefan
authors.initials: S
authors.lastname: Evers
authors.forename: Klaus
authors.initials: K
authors.lastname: Berger
authors.forename: Martin
authors.initials: M
authors.lastname: Marziniak
mesh_terms: D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014365:Tryptophan Hydroxylase / Q000235:genetics*
chemical_list: C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase