Association between interleukin-4 (IL-4), gene polymorphisms (C-589T, T+2979G, and C-33T) and migraine susceptibility in Iranian population: A case-control study

BackgroundMigraine is a chronic neurological disease characterized by recurrent moderate to severe headaches commonly in association with neuro-inflammation. Interleukin-4 (IL-4), an anti-inflammatory cytokine, plays an important role in modulating pain threshold and has an essential role in stimulation of pain receptors in the trigeminal nerve fibers.Aim of the studyThe current study aimed to investigate the possible associations between IL-4 single nucleotide polymorphisms (SNPs) and susceptibility to migraine in Iranian patients.Patients and methodsIn a prospective case-control study, we studied blood samples of 190 patients with migraine (migraineurs) and 200 healthy controls (HCs) for analysis of gene variants. Genotyping for the IL-4 SNPs: C-589T (rs2243250), T+2979G (rs2227284), and C-33T (rs2070874) were performed using PCR-RFLP. Statistical analysis was performed using the SPSS version 21.0 (SPSS, Chicago) and SNPStats version 1.14.0.Results and conclusionAmong IL-4 SNPs, rs2243250 (TC genotype, OR = 0.25, 95% CI = 0.13-0.50, P = 0.001) and rs2227284 (TG and TT genotypes, OR = 0.44, 95% CI = 0.23-0.92, P = 0.029 and OR = 0.38, 95% CI = 0.18-0.79, P = 0.009 respectively) were significantly associated with migraine. No significant associations between IL-4 SNP rs2070874 (TC, TT and CC genotypes) and migraine were found. The most frequent genotypes in the migraineurs were CC in both SNPs rs2243250 (79%), and rs2070874 (71.5%), as well as GG for SNP rs2227284 (64%). There was no statistically significant relationship between these SNPs and different subclasses (common, classic and complicated) of migraine. Our findings revealed that in IL-4 rs2243250 and rs2227284 genotypes and allele frequencies have a role in susceptibility to migraine in our population. Therefore, it is suggested that in addition to other factors, IL-4 genetic variations also play a pivotal role in the progress of migraine.