Genotype at the P554L variant of the hexose-6 phosphate dehydrogenase gene is associated with carotid intima-medial thickness

Simple item page
dc.contributor.authorRahman, Thahira Jen_ZA
dc.contributor.authorWalker, Elizabeth Aen_ZA
dc.contributor.authorMayosi, Bongani Men_ZA
dc.contributor.authorHall, Darroch Hen_ZA
dc.contributor.authorAvery, Peter Jen_ZA
dc.contributor.authorConnell, John M Cen_ZA
dc.contributor.authorWatkins, Hughen_ZA
dc.contributor.authorStewart, Paul Men_ZA
dc.contributor.authorKeavney, Bernarden_ZA
dc.date.accessioned2015-11-23T12:36:59Z
dc.date.available2015-11-23T12:36:59Z
dc.date.issued2011en_ZA
dc.description.abstractObjective The combined thickness of the intima and media of the carotid artery (carotid intima-medial thickness, CIMT) is associated with cardiovascular disease and stroke. Previous studies indicate that carotid intima-medial thickness is a significantly heritable phenotype, but the responsible genes are largely unknown. Hexose-6 phosphate dehydrogenase (H6PDH) is a microsomal enzyme whose activity regulates corticosteroid metabolism in the liver and adipose tissue; variability in measures of corticosteroid metabolism within the normal range have been associated with risk factors for cardiovascular disease. We performed a genetic association study in 854 members of 224 families to assess the relationship between polymorphisms in the gene coding for hexose-6 phosphate dehydrogenase (H6PD) and carotid intima-medial thickness. METHODS: Families were ascertained via a hypertensive proband. CIMT was measured using B-mode ultrasound. Single nucleotide polymorphisms (SNPs) tagging common variation in the H6PD gene were genotyped. Association was assessed following adjustment for significant covariates including "classical" cardiovascular risk factors. Functional studies to determine the effect of particular SNPs on H6PDH were performed. RESULTS: There was evidence of association between the single nucleotide polymorphism rs17368528 in exon five of the H6PD gene, which encodes an amino-acid change from proline to leucine in the H6PDH protein, and mean carotid intima-medial thickness (p = 0.00065). Genotype was associated with a 5% (or 0.04 mm) higher mean carotid intima-medial thickness measurement per allele, and determined 2% of the population variability in the phenotype. CONCLUSIONS: Our results suggest a novel role for the H6PD gene in atherosclerosis susceptibility.en_ZA
dc.identifier.apacitationRahman, T. J., Walker, E. A., Mayosi, B. M., Hall, D. H., Avery, P. J., Connell, J. M. C., ... Keavney, B. (2011). Genotype at the P554L variant of the hexose-6 phosphate dehydrogenase gene is associated with carotid intima-medial thickness. <i>PLoS One</i>, http://hdl.handle.net/11427/15349en_ZA
dc.identifier.chicagocitationRahman, Thahira J, Elizabeth A Walker, Bongani M Mayosi, Darroch H Hall, Peter J Avery, John M C Connell, Hugh Watkins, Paul M Stewart, and Bernard Keavney "Genotype at the P554L variant of the hexose-6 phosphate dehydrogenase gene is associated with carotid intima-medial thickness." <i>PLoS One</i> (2011) http://hdl.handle.net/11427/15349en_ZA
dc.identifier.citationRahman, T. J., Walker, E. A., Mayosi, B. M., Hall, D. H., Avery, P. J., Connell, J. M., ... & Keavney, B. (2011). Genotype at the P554L variant of the hexose-6 phosphate dehydrogenase gene is associated with carotid intima-medial thickness. PloS one, 6(8), e23248-e23248. doi:10.1371/journal.pone.0023248en_ZA
dc.identifier.ris TY - Journal Article AU - Rahman, Thahira J AU - Walker, Elizabeth A AU - Mayosi, Bongani M AU - Hall, Darroch H AU - Avery, Peter J AU - Connell, John M C AU - Watkins, Hugh AU - Stewart, Paul M AU - Keavney, Bernard AB - Objective The combined thickness of the intima and media of the carotid artery (carotid intima-medial thickness, CIMT) is associated with cardiovascular disease and stroke. Previous studies indicate that carotid intima-medial thickness is a significantly heritable phenotype, but the responsible genes are largely unknown. Hexose-6 phosphate dehydrogenase (H6PDH) is a microsomal enzyme whose activity regulates corticosteroid metabolism in the liver and adipose tissue; variability in measures of corticosteroid metabolism within the normal range have been associated with risk factors for cardiovascular disease. We performed a genetic association study in 854 members of 224 families to assess the relationship between polymorphisms in the gene coding for hexose-6 phosphate dehydrogenase (H6PD) and carotid intima-medial thickness. METHODS: Families were ascertained via a hypertensive proband. CIMT was measured using B-mode ultrasound. Single nucleotide polymorphisms (SNPs) tagging common variation in the H6PD gene were genotyped. Association was assessed following adjustment for significant covariates including "classical" cardiovascular risk factors. Functional studies to determine the effect of particular SNPs on H6PDH were performed. RESULTS: There was evidence of association between the single nucleotide polymorphism rs17368528 in exon five of the H6PD gene, which encodes an amino-acid change from proline to leucine in the H6PDH protein, and mean carotid intima-medial thickness (p = 0.00065). Genotype was associated with a 5% (or 0.04 mm) higher mean carotid intima-medial thickness measurement per allele, and determined 2% of the population variability in the phenotype. CONCLUSIONS: Our results suggest a novel role for the H6PD gene in atherosclerosis susceptibility. DA - 2011 DB - OpenUCT DO - 10.1371/journal.pone.0023248 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2011 T1 - Genotype at the P554L variant of the hexose-6 phosphate dehydrogenase gene is associated with carotid intima-medial thickness TI - Genotype at the P554L variant of the hexose-6 phosphate dehydrogenase gene is associated with carotid intima-medial thickness UR - http://hdl.handle.net/11427/15349 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15349
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0023248
dc.identifier.vancouvercitationRahman TJ, Walker EA, Mayosi BM, Hall DH, Avery PJ, Connell JMC, et al. Genotype at the P554L variant of the hexose-6 phosphate dehydrogenase gene is associated with carotid intima-medial thickness. PLoS One. 2011; http://hdl.handle.net/11427/15349.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDepartment of Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2011 Rahman et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherAtherosclerosisen_ZA
dc.subject.otherBlood pressureen_ZA
dc.subject.otherGenotypingen_ZA
dc.subject.otherAllelesen_ZA
dc.subject.otherVariant genotypesen_ZA
dc.subject.otherHypertensionen_ZA
dc.subject.otherPhosphatesen_ZA
dc.subject.otherSequence alignmenten_ZA
dc.titleGenotype at the P554L variant of the hexose-6 phosphate dehydrogenase gene is associated with carotid intima-medial thicknessen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Rahman_Genotype_P554L_Variant_2011.pdf
Size:
323.56 KB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Journal Articles