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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

Nourollah Ramroodi
Mohammad Reza Javan
Nima Sanadgol
Mehdi Jahantigh
Tooba Nakhzari Khodakheir
Nasrin Ranjbar


Background: Migraine 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 study: The current study aimed to investigate the possible associations between IL-4 single nucleotide polymorphisms (SNPs) and susceptibility to migraine in Iranian patients.

Patients and methods: In 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 conclusion: Among 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.

Keywords: IL-4; Migraine; RFLP-PCR; Genotyping; Neuro-inflammation; Headache

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eISSN: 1110-8630