Abstract
Migraine without aura (MWOA) and migraine with aura (MWA) are disorders in which multiple factors, including environmental and genetic factors, are involved. In a previous study we hypothesized a protective role of HLA-DR2 antigen, providing additional basis for the proposed genetic heterogeneity between MWOA and MWA. The cytokines TNFA and TNFB are polypeptide effectors of inflammatory reaction and endothelial function. To better define the involvement of HLA region genes in migraine, we performed an association study of the tumor necrosis factor (TNF) genes, located in the HLA class III region, with MWOA and MWA. TNFB alleles 1 and 2 were analyzed by PCR-RFLP in 30 MWOA patients, in 47 MWA patients and in 101 random controls. The frequency of TNFB*2 was significantly increased in MWOA patients as compared with controls (78.72% vs. 61.4%, p(c) = 0.004), while no significant differences were found between MWA patients and controls. The distribution of TNFB genotypic frequencies showed a significant decrease of TNFB 1,1 homozygotes in MWOA patients (p(c) = 0.0201). The observed increase of TNFB*2 in MWOA is dustributed in TNFB 2,2 and TNFB 1,2 genotypes, meaning that the susceptibility allele could act as “dominant”: people with TNFB 1,1 genotype are less predisposed to the disease. While more studies are needed in larger migraine samples to reinforce the statistical power of the reported data, the present study supports the hypothesis that TNFB is a susceptibility gene in MWOA.