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J Clin Neurol. 2012 Dec;8(4):301-4. doi: 10.3988/jcn.2012.8.4.301. Epub 2012 Dec 21.

Association between the G252A Tumor Necrosis Factor-β Gene Polymorphism and Medication-Overuse Headache.

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Department of Pathophysiology, Showa University School of Pharmacy, Tokyo, Japan.



Migraine patients are particularly prone to the complication of medication-overuse headache (MOH). Although it has been shown that A allele carriers for the tumor necrosis factor (TNF)-β gene G252A polymorphism are at high risk of the development of migraine without aura, the relationship between the TNF-β gene G252A polymorphism and MOH is unknown. We investigated whether the TNF-β gene G252A polymorphism is involved in the aggravation of migraine by overuse of medications.


Forty-seven migraine patients (6 males and 41 females; age 36.4±10.3 years, mean±SD) and 22 MOH patients (1 male and 21 females; age 39.6±9.9 years) who had migraine were included in this study. The genotype for the TNF-β gene G252A polymorphism was determined by polymerase-chain-reaction restriction-fragment-length polymorphism analysis.


The distribution of TNF-β gene G252A genotype frequency differed significantly between migraine and MOH patients (p=0.013). The G/G genotype was carried by 23% of the migraine patients but it was absent in MOH patients.


G/G genotype carriers appear to be less susceptible to the aggravation of migraine by overuse of medications. The G252A TNF-β gene polymorphism may be one of the factors contributing to the complications of MOH in patients with migraine.


medication overuse headache; migraine; tumor necrosis factor gene

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