We investigated whether polymorphisms of the endothelial nitric oxide synthase (eNOS), neuronal NOS (nNOS), and GTP cyclohydrolase I (GTPCH) genes are involved in the aggravation of migraine induced by overuse of medications. We studied 47 patients with migraine (six males and 41 females; 36.4 ± 10.3 years of age) and 22 patients with migraine exhibiting medication overuse headache (MOH, one male and 21 females; 39.6 ± 9.9 years of age). The genotypes of polymorphisms of the eNOS (rs1799983), nNOS (rs2682826), and GTPCH (rs841) genes were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The genotypic distributions of rs2682826 (T/T plus T/C vs. C/C, P = 0.254), rs1799983 (G/G vs. G/T plus T/T, P = 1.000), and rs841 (T/T plus T/C vs. C/C, P = 0.149) were not significantly different between patients with migraine and patients with MOH. The results of this study showed an absence of association between the polymorphisms of eNOS, nNOS, and GTPCH genes and the complication of MOH in patients with migraine.

BACKGROUND AND PURPOSE: 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)-beta gene G252A polymorphism are at high risk of the development of migraine without aura, the relationship between the TNF-beta gene G252A polymorphism and MOH is unknown. We investigated whether the TNF-beta gene G252A polymorphism is involved in the aggravation of migraine by overuse of medications. METHODS: 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-beta gene G252A polymorphism was determined by polymerase-chain-reaction restriction-fragment-length polymorphism analysis. RESULTS: The distribution of TNF-beta 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. CONCLUSIONS: G/G genotype carriers appear to be less susceptible to the aggravation of migraine by overuse of medications. The G252A TNF-beta gene polymorphism may be one of the factors contributing to the complications of MOH in patients with migraine.
Alleles ; Genotype ; Headache ; Humans ; Lymphotoxin-alpha ; Male ; Migraine Disorders ; Migraine without Aura ; Tumor Necrosis Factor-alpha