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Byline: Shahir Mazaheri (1), Mehrdad Hajilooi (2), Alireza Rafiei (3) Keywords: polymorphism; genetics; tumor necrosis factor-[alpha]; migraine without aura Abstract: Migraine is considered to be a polygenic multifactorial disease with various environmental and genetic etiologies. Tumor necrosis factor-alpha (TNF-[alpha]), a potent immunomodulator and pro-inflammatory cytokine, has been implicated in many pathological processes in brain. The hypothesis of this study was that migraine without aura (MWA) might be associated with TNF-[alpha] (-308) polymorphism, resulting in increased TNF-[alpha] production. Genotyping was performed on DNA extracted from peripheral leukocytes by PCR--SSP method in 221 patients with WMA and 183 healthy control subjects from Iranian population. The results showed that the frequency of -308 A variant allele was higher in MWA than in the control group (40.6% versus 22.3%, OR 3.73, 95% CI 2.4--5.82, p &lt 0.0001). TNF-[alpha] GA heterozygous genotype, high producer, was significantly more prevalent in patients with MWA than controls (74% versus 44.7%, p &lt 0.0001) whilst the low producer GG homozygous genotype was less frequent in patients compared with controls (22.4% versus 55.3%, p &lt 0.0001). The logistic regression analysis showed a significant association for TNF-[alpha] (-308A) female allele carriers with MWA at reproductive ages (OR 2.56 95% CI, 1.57--4.16, p &lt 0.0001) when compared with their matched control subjects. In conclusion, this study demonstrates an association of tumor necrosis factor-alpha (-308A) carriage with MWA, suggesting that carrying a high responder TNF-alpha-308A allele may be a genetic factor in increasing the susceptibility to develop MWA. Author Affiliation: (1) Dept. of Neurology, Sina Hospital, Hamadan University of Medical Sciences, Hamadan, Iran (2) Dept. of Immunology, Molecular Medicine Research Center, Hamadan University of Medical Sciences, Hamadan, Iran (3) Dept. of Immunology and Microbiology, Sari Medical School, Mazandaran University of Medical Sciences, Sari, Iran Article History: Registration Date: 01/01/2006 Received Date: 04/12/2005 Accepted Date: 19/04/2006 Online Date: 24/10/2006 Article note: M. Hajilooi and A. Rafiei contributed equally to this work. Received in revised form: 10 April 2006