A population genomics overview of the neuronal nitric oxide synthase (nNOS) gene and its relationship to migraine susceptibility

Johnson , M.P., Lea, R.A., Colson, N.J., MacMillan, J.C., & Griffiths, L.R. (2005) A population genomics overview of the neuronal nitric oxide synthase (nNOS) gene and its relationship to migraine susceptibility. Cellular and Molecular Biology, 51(3), pp. 285-292.

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The ubiquitous chemical messenger molecule nitric oxide (NO) has been implicated in a diverse range of biological activities including neurotransmission, smooth muscle motility and mediation of nociception. Endogenous synthesis of NO by the neuronal isoform of the nitric oxide synthase gene family has an essential role within the central and peripheral nervous systems in addition to the autonomic innervation of cerebral blood vessels. To investigate the potential role of NO and more specifically the neuronal nitric oxide synthase (nNOS) gene in migraine susceptibility, we investigated two microsatellite repeat variants residing within the 5′ and 3′ regions of the nNOS gene. Population genomic evaluation of the two nNOS repeat variants indicated significant linkage disequilibrium between the two loci. Z-DNA conformational sequence structures within the 5′ region of the nNOS gene have the potential to enhance or repress gene promoter activity. We suggest that genetic analysis of this 5′ repeat variant is the more functional variant expressing gene wide information that could affect endogenous NO synthesis and potentially result in diseased states. However, no association with migraine (with or without aura) was seen in our extensive case-control cohort (n = 579 affected with matched controls), when both the 5′ and 3′ genetic variants were investigated.

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ID Code: 63130
Item Type: Journal Article
Refereed: Yes
Additional Information: 16191396
Keywords: Association, Haplotype, Linkage disequilibrium, Migraine, nNOS, microsatellite DNA, neuronal nitric oxide synthase, nitric oxide, nitric oxide synthase, article, autonomic innervation, brain blood vessel, central nervous system, controlled study, disease predisposition, DNA conformation, gene activity, gene function, gene linkage disequilibrium, gene locus, gene structure, genetic susceptibility, genetic variability, genomics, human, major clinical study, migraine, migraine aura, neurotransmission, nociception, peripheral nervous system, population research, promoter region, smooth muscle contractility, 3' Flanking Region, 5' Flanking Region, Alleles, Case-Control Studies, Cohort Studies, DNA, Z-Form, Exons, Female, Gene Expression Regulation, Enzymologic, Genetic Predisposition to Disease, Haplotypes, Humans, Isoenzymes, Linkage Disequilibrium, Male, Microsatellite Repeats, Migraine Disorders, Nitric Oxide, Nitric Oxide Synthase Type I, Promoter Regions (Genetics)
ISSN: 1455-680
Divisions: Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2005 Elsevier Inc.
Deposited On: 04 Oct 2013 01:20
Last Modified: 02 Jul 2014 22:47

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