OBJECTIVE: Aim of this study was to investigate whether functional polymorphisms in the IL-1 family (IL-1??, IL-1?? and IL-1RN), and TNF-?? genes may influence the response to oral nonsteroidal anti-inflammatory drugs (NSAIDs) administration during migraine attacks. BACKGROUND: At present, frontline therapies in migraine acute treatment include NSAIDs and triptans. However, a significant portion of treated patients do not obtain consistent pain relief. Several studies suggested a role for proinflammatory cytokines in the pathophysiology of migraine. DESIGN/METHODS: 313 consecutive patients (96 men, 217 women) with episodic migraine without aura (IHCD-II criteria) were recruited at the Headache Center, Department of Neuroscience, University of Torino, Italy. During the first visit, migraineurs were prescribed NSAIDs and were given a headache diary in order to record the clinical response in three consecutive migraine attacks. A positive response was defined by having a decrease of ???2 points in a 4-point scale intensity of pain, after 120 minutes NSAIDs administration, in at least two attacks out of three. Patients were genotyped for functional polymorphisms in the following genes: IL-1?? (-889 C>T), IL-1?? (-511 C>T), IL-1?? (+3953 C>T), IL-1RN (VNTR), and TNF-?? (-308 G>A). RESULTS: Migraine patients carrying the A allele of the TNF-?? promoter -308 A/G polymorphism showed a significant association with a lack of efficacy after NSAIDs administration in migraine attacks compared to the G allele (p< 0.01, OR 2.74, 95 % CI: 1.19 ??? 6.29). Remaining polymorphisms had no significant effect. CONCLUSIONS: Our study showed that a functional polymorphism in the TNF-?? gene modulates the clinical response to NSAIDs administration in acute migraine attacks. Patients with a higher production of the active cytokine during stress showed a significantly lower anti-migraine effects. Additional studies are needed to further deepen these findings.
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