Variants in the human potassium channel gene (KCNN3) are associated with migraine in a high risk genetic isolate

The calcium-activated potassium ion channel gene (KCNN3) is located in the vicinity of the familial hemiplegic migraine type 2 locus on chromosome 1q21.3. This gene is expressed in the central nervous system and plays a role in neural excitability. Previous association studies have provided some, al...

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Bibliographic Details
Published in:Journal of headache and pain 2011-12, Vol.12 (6), p.603-608
Main Authors: Cox, Hannah C., Lea, Rod A., Bellis, Claire, Carless, Melanie, Dyer, Tom, Blangero, John, Griffiths, Lyn R.
Format: Article
Language:English
Subjects:
Adult
Aged
Female
Genes
Genetic Predisposition to Disease - genetics
Genetic Variation - genetics
Humans
Indexing in process
Internal Medicine
Male
Medicine
Medicine & Public Health
Middle Aged
Migraine
Migraine Disorders - genetics
Migraine Disorders - metabolism
Migraine Disorders - physiopathology
Neurology
Original
Pain Medicine
Pedigree
Polymorphism, Single Nucleotide - genetics
Small-Conductance Calcium-Activated Potassium Channels - genetics
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Summary:The calcium-activated potassium ion channel gene (KCNN3) is located in the vicinity of the familial hemiplegic migraine type 2 locus on chromosome 1q21.3. This gene is expressed in the central nervous system and plays a role in neural excitability. Previous association studies have provided some, although not conclusive, evidence for involvement of this gene in migraine susceptibility. To elucidate KCNN3 involvement in migraine, we performed gene-wide SNP genotyping in a high-risk genetic isolate from Norfolk Island, a population descended from a small number of eighteenth century Isle of Man ‘Bounty Mutineer’ and Tahitian founders. Phenotype information was available for 377 individuals who are related through the single, well-defined Norfolk pedigree (96 were affected: 64 MA, 32 MO). A total of 85 SNPs spanning the KCNN3 gene were genotyped in a sub-sample of 285 related individuals (76 affected), all core members of the extensive Norfolk Island ‘Bounty Mutineer’ genealogy. All genotyping was performed using the Illumina BeadArray platform. The analysis was performed using the statistical program SOLAR v4.0.6 assuming an additive model of allelic effect adjusted for the effects of age and sex. Haplotype analysis was undertaken using the program HAPLOVIEW v4.0. A total of four intronic SNPs in the KCNN3 gene displayed significant association ( P  
ISSN:1129-2369
1129-2377
DOI:10.1007/s10194-011-0392-7