Investigation of the NOTCH3 and TNFSF7 Genes on C19p13 as Candidates for Migraine



Robert A Smith1, Robert Curtain1, Mick Ovcaric1, Lotti Tajouri1, John MacMillan2, Lyn Griffiths1, *
1 Genomics Research Centre, School of Medical Science, Griffith University, Gold Coast, Queensland, Australia
2 Queensland Clinical Genetics Service, Royal Children’s Hospital Health Service District, Brisbane, Queensland, Australia


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©Smith et al.; Licensee Bentham Open.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

* Address correspondence to this author at the Genomics Research Centre, School of Medical Science, Griffith University Gold Coast, Queensland, 4222, Australia; E-mail: l.griffiths@griffith.edu.au


Abstract

To investigate the migraine locus around the C19p13 region through analysis of the NOTCH3 gene (C19p13.2-p13.1), previously shown to be a gene involved in CADASIL and the TNFSF7 gene (C19p13), homologous to the ligands of TNF-alpha and TNF-beta, genes that have previously been associated with migraine. The NOTCH3 gene was analysed by sequencing all exons with known CADASIL mutations in a typical (non-familial hemiplegic) migraine family (MF1) that has previously been shown to be linked to C19p13. The TNFSF7 gene was investigated through SNP association analysis using a matched case-control migraine population. NOTCH3 gene sequencing results for affected members of MF1 proved to be negative for all known sequence variants giving rise to mutations for CADASIL. TNFSF7 gene chi-square results showed non-significant P values across all populations tested against controls, except for the MO subgroup which displayed a possible association with the TNFSF7 SNP (genotype, allele analysis P = 0.036, P = 0.017 respectively). Our results suggest that common migraine is not caused by any known CADASIL mutations in the NOTCH3 gene of interest. However, the TNFSF7 gene displayed signs of involvement in a MO affected population and indicates that further independent studies of this marker are warranted.

Keywords: Typical migraine, NOTCH3, CADASIL, TNFSF7, C19p13, MO.