Journal
CEPHALALGIA
Volume 32, Issue 3, Pages 203-212Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/0333102411433300
Keywords
Migraine; STX1A; genetics; ion channels; SNP
Categories
Funding
- Austrian National Bank [10645]
- AstraZeneca (Austria)
- Linde Gas (Austria)
- A. Menarini Pharma GmbH (Austria)
- Pfizer (Austria)
- Medical Research Council [G9817803B] Funding Source: researchfish
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Objectives: To examine the association of genetic variants in the syntaxin 1A gene (STX1A) with common forms of migraine, and perform a combined analysis of the data from the current study and previously published reports. Methods: We investigated the parent-to-offspring transmission of rs6951030, rs4363087 and rs2293489 in 191 family trios, each with a proband with childhood-onset migraine, and performed a case-control analysis between the probands and 223 unrelated controls. In addition, we performed a combined data analysis with an overall sample of 567 migraine patients and 720 unrelated controls and performed a migraine-specific gene-network analysis. Results: The transmission disequilibrium test revealed significant transmission distortion of rs4363087 in migraine overall (OR = 1.56, p = 0.006; p = 0.01 after correction for multiple testing) and migraine without aura (OR = 1.58, p = 0.01; corrected p = 0.04). Two-marker haplotype analysis revealed transmission distortion of A-G (rs6951030-rs4363087; OR = 1.47, p = 0.01) and A-C (rs4363087-rs2293489; OR = 0.66, p = 0.01). Combined analysis showed significant association of rs941298 with migraine overall (OR = 1.28, p = 0.004) and migraine without aura (OR = 1.3, p = 0.008). Network analysis identified 24 genes relating STX1A to other migraine candidate genes, including KCNK18 (TRESK channel) involved in the cytoplasmatic calcium signalling together with syntaxin 1A. Conclusion: Our results provide support for the hypothesis that STX1A represents a susceptibility gene for migraine.
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