EXCLUSION OF 5-HT2A AND 5-HT2C RECEPTOR GENES AS CANDIDATE GENES FOR MIGRAINE

Several lines of investigation suggest that the serotonergic system ma y be involved in the pathoganesis of migraine. In particular, drugs wh ich block 5-HT2 receptor subtypes appear to be effective migraine prop hylactic agents. Therefore, chromosomal DNA regions overlapping the 5- HT2A (13q14-q22) and 5 HT2C (Xq22-25) receptor loci were analyzed for possible linkage to the clinical diagnosis of migraine. No evidence fo r linkage to either chromosomal region was found, although a small sub set of migrainous families showed positive likelihood of odds (LOD) sc ores. However, a homogeneity (HOMOG) analysis provided no statistical evidence for locus heterogeneity. The coding region of the 5-HT2A and 5-HT2C receptor genes was also analyzed in migraine patients and unaff ected controls using polmerase chain reaction and direct sequencing. N o mutations were found in the deduced amino acid sequence of either re ceptor in the sample of migraineurs tested. These results indicate tha t DNA-based mutations in the 5-HT2A and 5-HT2C receptors are not gener ally involved in the pathogenesis of migraine.