Analysis of NOS Gene Polymorphisms in Relation to Cluster Headache and Predisposing Factors in Sweden.

Cluster headache is characterized by activation of the autonomic-trigeminal reflex. Nitric oxide can trigger headaches in patients, and nitric oxide signaling is known to be affected in cluster headache. Based on the hypothesis of nitric oxide being involved in cluster headache pathophysiology we investigated nitric oxide synthases as potential candidate genes for cluster headache. We analyzed eight variants in the three forms of nitric oxide synthase () genes, inducible (), endothelial () and neuronal (), and tested for association with cluster headache. Swedish cluster headache patients ( = 542) and controls ( = 581) were genotyped using TaqMan assays on an Applied Biosystems 7500 qPCR cycler. This is the largest performed genetic study on involvement in cluster headache so far. We found an association between cluster headache and one haplotype consisting of the minor alleles of rs2297518 and rs2779249 ( = 0.022). In addition, one of the analyzed variants, rs2682826, was associated with reported triptan use ( = 0.039). Our data suggest that genetic variants in genes do not have a strong influence on cluster headache pathophysiology, but that certain combinations of genetic variants in genes may influence the risk of developing the disorder or triptan use.