No evidence for involvement of the human inducible nitric oxide synthase (iNOS) gene in susceptibility to typical migraine

Migraine is a debilitating disorder affecting approximately 12% of Caucasia n populations. The disease has a large genetic component, although at prese nt the type and number of genes involved is unclear. Candidate gene studies may be useful strategies for identifying genes involved in complex disease s such as migraine, especially if the gene being examined contributes only a minor effect to the overall phenotype, Nitric oxide (NO) is emerging as a key molecule affecting the pain associated with migraine. Since NO synthas e (NOS) enzymes catalyze the synthesis of NO, the genes that code for these enzymes are good candidates for migraine molecular genetic analysis. This study investigated the role of a functionally relevant bi-allelic tetranucl eotide polymorphism located in the promoter region of the human inducible n itric oxide synthase (iNOS) gene in migraine etiology. A large group of mig raine affected individuals (n = 261) were genotyped and compared with an ag e- and sex-matched group of unaffected controls (n = 252). Results of a chi -squared analysis indicated that allele distributions for both migraine cas es and controls were not significantly different (chi (2) = 1.93, P = 0.16) . These findings offer no evidence for an allelic association of the tested iNOS polymorphism with the common forms of the disease and therefore do no t support a role for this gene in migraine pathogenesis, Am. J. Med. Genet. (Neuropsychiatr. Genet.) 105:110-113, 2001. (C) 2001 Wiley-Liss, Inc.