title: Association study of calcitonin gene-related polypeptide-alpha (CALCA) gene polymorphism with migraine.
abstract: Migraine is a neurological disorder that is associated with increased levels of calcitonin gene-related peptide (CGRP) in plasma. CGRP, being one of the mediators of neurogenic inflammation and a phenomenon implicated in the pathogenesis of migraine headache, is thus suggested to have an important role in migraine pathophysiology. Polymorphisms of the CALCA gene have been linked to Parkinson's disease, ovarian cancer and essential hypertension, suggesting a functional role for these polymorphisms. Given the strong evidence linking CGRP and migraine, it is hypothesised that polymorphisms in the CALCA gene may play a role in migraine pathogenesis. Seemingly non functional intronic polymorphisms are capable of disrupting normal RNA processing or introducing a splice site in the transcript. A 16bp deletion in the first intron of the CALCA gene has been reported to be a good match for the binding site for a transcription factor expressed strongly in neural crest derived cells, AP-2. This deletion also eliminates an intron splicing enhancer (ISE) that may potentially cause exon skipping. This study investigated the role of the 16bp intronic deletion in the CALCA gene in migraineurs and matched control individuals. Six hundred individuals were genotyped for the deletion by polymerase chain reaction followed by fragment analysis on the 3130 Genetic Analyser. The results of this study showed no significant association between the intronic 16bp deletion in the CALCA gene and migraine in the tested Australian Caucasian population. However, given the evidence linking CGRP and migraine, further investigation of variants with this gene may be warranted.
authors.affiliation: Genomics Research Centre and Griffith Health Institute, Griffith University Gold Coast, Parklands Drive, Southport, Queensland, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Menon
authors.forename: J
authors.initials: J
authors.lastname: Buteri
authors.forename: B
authors.initials: B
authors.lastname: Roy
authors.forename: M
authors.initials: M
authors.lastname: Murrell
authors.forename: S
authors.initials: S
authors.lastname: Quinlan
authors.forename: J C
authors.initials: JC
authors.lastname: Macmillan
authors.forename: R A
authors.initials: RA
authors.lastname: Lea
authors.forename: L M
authors.initials: LM
authors.lastname: Haupt
authors.forename: L R
authors.initials: LR
authors.lastname: Griffiths
mesh_terms: D001315:Australia; D002116:Calcitonin / Q000235:genetics*; D015740:Calcitonin Gene-Related Peptide; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011498:Protein Precursors / Q000235:genetics*
chemical_list: C000606589:CALCA protein, human; D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide