Association study of the serotoninergic system in migraine in the spanish population

In order to evaluate the contribution of 19 serotonin‐related genes to the susceptibility to migraine in a Spanish population we performed a case–control association study of 122 single nucleotide polymorphisms (SNPs), selected according to genetic coverage parameters, in 528 migraine patients —308 with migraine without aura (MO) and 220 with migraine with aura (MA)— and 528 sex‐matched migraine‐free controls. The single‐marker analysis identified nominal associations with the migraine phenotype or with the MO or MA subtypes. The multiple‐marker analysis revealed risk haplotypes in three genes that remained significantly associated with migraine after correction by permutations. Two‐marker risk haplotypes were identified in the HTR2B (rs16827801T‐rs10194776G) and MAOA (rs3027400G‐rs2072743C) genes conferring susceptibility to MO, and a four‐marker haplotype in DDC was specific of MA (rs2329340A‐rs11974297C‐rs2044859T‐rs11761683G). The present study supports the involvement of HTR2B and MAOA genes in the genetic predisposition to MO, while DDC might confer susceptibility to MA. These results suggest a differential involvement of serotonin‐related genes in the genetic background of MO and MA. © 2009 Wiley‐Liss, Inc.