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.