Journal
BRAIN SCIENCES
Volume 11, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/brainsci11010034
Keywords
nitric oxide; nitric oxide synthase; neurovascular; smoking; haplotype
Categories
Funding
- Swedish Brain Foundation
- Swedish Research Council [FO2019-0004]
- Marta Lundqvists stiftelse
- Karolinska Institutet Foundation [2018-01738]
- Mellby Gard Foundation [FO2019-0004, FO2018-0008]
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A study on the involvement of NOS genes in cluster headache revealed an association between an iNOS haplotype and the disorder, as well as an association between an nNOS variant and reported triptan use. This suggests that while genetic variants in NOS genes may not strongly influence cluster headache pathophysiology, specific combinations of these variants could impact the risk of developing the disorder or using triptans.
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 (NOS) genes, inducible NOS (iNOS), endothelial NOS (eNOS) and neuronal NOS (nNOS), and tested for association with cluster headache. Swedish cluster headache patients (n = 542) and controls (n = 581) were genotyped using TaqMan(R) assays on an Applied Biosystems 7500 qPCR cycler. This is the largest performed genetic study on NOS involvement in cluster headache so far. We found an association between cluster headache and one iNOS haplotype consisting of the minor alleles of rs2297518 and rs2779249 (p = 0.022). In addition, one of the analyzed nNOS variants, rs2682826, was associated with reported triptan use (p = 0.039). Our data suggest that genetic variants in NOS genes do not have a strong influence on cluster headache pathophysiology, but that certain combinations of genetic variants in NOS genes may influence the risk of developing the disorder or triptan use.
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