Migraine, a highly prevalent headache disorder, is regarded as a polygenic multifactorial disease. Single-nucleotide polymorphisms(SNPs) in the genes that involved in sex hormone metabolism may comprise risk for migraine, but the results ofprevious genetic association studies are conflicting. The aim of this study was to evaluate genetic variants in genes involved inoestrogen receptor and oestrogen hormone metabolism in a Turkish population. A total of 12 SNPs in the ESR1, ESR2, FSHR,
CYP19A1, SHBG and NRIP1 genes were genotyped in 142 migraine cases and 141 nonmigraine controls, using a BioMark96.96 dynamic array system. In addition, gene–gene interactions were analysed using generalized multifactor dimensionalityreduction (GMDR) methods. According to GMDR analysis, our results indicated that there was a significant associationbetween migraine and gene–gene interaction among the CYP19A1, FSHR, ESR1 and NRIP1. Single-gene variant analysisshowed that a significant association was observed between the TT genotype of rs10046 and migraine susceptibility.When theanalysis was performed only in women, the GG genotype of rs2229741 was different between migraineurs and controls. Whenthe female migraine patients were divided into two groups, migraine related to menstruation (MRM) or migraine not relatedto menstruation (MNRM), GG genotype of rs726281 was significantly associated with MRM. These results suggested thatrs10046 could play a potential role in migraine susceptibility in Turkish population. Also, the rare GG genotype of rs726281appears to influence migraine susceptibility in a recessive manner in MRM subgroup of female patients. In addition, variantGG genotype of rs2229741 may reduce the risk of migraine in Turkish women.