Correlation between iron regulatory protein-1 (G-32373708A) and -2 (G-49520870A), gene variations and migraine susceptibility in southeast Iran: A case-control study

Migraine is a chronic neurological disease characterized by recurrent moderate to severe headaches commonly in association with neuro-inflammation. Iron regulatory proteins (IRPs) regulate the expression of iron metabolism genes and control cytosolic iron concentrations in order to optimize cellular iron availability. The current study aimed to investigate the possible associations IRP-1 and -2 single nucleotide polymorphisms (SNPs) and susceptibility to migraine in Iranian patients. In a prospective case-control study, we studied blood samples of 190 patients with migraine and 200 healthy controls for analysis of gene variants. Genotyping for the IRP-1 SNP: G-32373708A (rs867469), and IRP-2 SNP: G-49520870A (rs17483548) were performed using PCR-ASO and PCR-RFLP respectively. Statistical analysis was performed using the SPSS version 21.0 (SPSS, Chicago) and SNPStats version 1.14.0. Among IRP SNPs, rs867469 (GG genotype, adjusted OR = 3.82, 95% CI = 1.131-12.953, P = 0.031) and rs17483548 (GG genotype, adjusted OR = 19.12, 95% CI = 3.69-99.05, P = 0.001) were significantly associated with migraine. The most frequent genotypes in the migraineurs were GA in both SNPs rs867469 (58%), and rs17483548 (68%). Moreover, there was significant statistically relationship between rs17483548 SNP (GG genotype, adjusted OR = 0.10, 95% CI = 0.013-0.745, P = 0.025) and different subclasses (without and with aura) of migraine. Our data indicated that G/G genotypes in both the G-32373708A-IRP-1 and G-49520870A-IRP-2 polymorphisms could be associated with increased risk for migraine. Therefore, it is suggested that in addition to other factors, IRP-1 and IRP-2SNPs may play a pivotal role in the migraine.