STK39 polymorphisms and blood pressure: an association study in British Caucasians and assessment of cis-acting influences on gene expression

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dc.contributor.authorCunnington, Michael Sen_ZA
dc.contributor.authorKay, Chrisen_ZA
dc.contributor.authorAvery, Peteren_ZA
dc.contributor.authorMayosi, Bonganien_ZA
dc.contributor.authorKoref, Mauroen_ZA
dc.contributor.authorKeavney, Bernarden_ZA
dc.date.accessioned2015-10-30T09:34:31Z
dc.date.available2015-10-30T09:34:31Z
dc.date.issued2009en_ZA
dc.description.abstractBACKGROUND:Blood pressure (BP) has significant heritability, but the genes responsible remain largely unknown. Single nucleotide polymorphisms (SNPs) at the STK39 locus were recently associated with hypertension by genome-wide association in an Amish population; in vitro data from transient transfection experiments using reporter constructs suggested that altered STK39 expression might mediate the effect. However, other large studies have not implicated STK39 in hypertension. We determined whether reported SNPs influenced STK39 expression in vivo, or were associated with BP in a large British Caucasian cohort. METHODS: 1372 members of 247 Caucasian families ascertained through a hypertensive proband were genotyped for reported risk variants in STK39 (rs6749447, rs3754777, rs35929607) using Sequenom technology. MERLIN software was used for family-based association testing. Cis-acting influences on expression were assessed in vivo using allelic expression ratios in cDNA from peripheral blood cells in 35 South African individuals heterozygous for a transcribed SNP in STK39 (rs1061471) and quantified by mass spectrometry (Sequenom). RESULTS: No significant association was seen between the SNPs tested and systolic or diastolic BP in clinic or ambulatory measurements (all p > 0.05). The tested SNPs were all associated with allelic expression differences in peripheral blood cells (p < 0.05), with the most significant association for the intronic SNP rs6749447 (P = 9.9 x 10-4). In individuals who were heterozygous for this SNP, on average the G allele showed 13% overexpression compared to the T allele. CONCLUSIONS: STK39 expression is modified by polymorphisms acting in cis and the typed SNPs are associated with allelic expression of this gene, but there is no evidence for an association with BP in a British Caucasian cohort.en_ZA
dc.identifier.apacitationCunnington, M. S., Kay, C., Avery, P., Mayosi, B., Koref, M., & Keavney, B. (2009). STK39 polymorphisms and blood pressure: an association study in British Caucasians and assessment of cis-acting influences on gene expression. <i>BMC Medical Genetics</i>, http://hdl.handle.net/11427/14529en_ZA
dc.identifier.chicagocitationCunnington, Michael S, Chris Kay, Peter Avery, Bongani Mayosi, Mauro Koref, and Bernard Keavney "STK39 polymorphisms and blood pressure: an association study in British Caucasians and assessment of cis-acting influences on gene expression." <i>BMC Medical Genetics</i> (2009) http://hdl.handle.net/11427/14529en_ZA
dc.identifier.citationCunnington, M. S., Kay, C., Avery, P. J., Mayosi, B. M., Koref, M. S., & Keavney, B. (2009). STK39 polymorphisms and blood pressure: an association study in British Caucasians and assessment of cis-acting influences on gene expression. BMC medical genetics, 10(1), 135.en_ZA
dc.identifier.ris TY - Journal Article AU - Cunnington, Michael S AU - Kay, Chris AU - Avery, Peter AU - Mayosi, Bongani AU - Koref, Mauro AU - Keavney, Bernard AB - BACKGROUND:Blood pressure (BP) has significant heritability, but the genes responsible remain largely unknown. Single nucleotide polymorphisms (SNPs) at the STK39 locus were recently associated with hypertension by genome-wide association in an Amish population; in vitro data from transient transfection experiments using reporter constructs suggested that altered STK39 expression might mediate the effect. However, other large studies have not implicated STK39 in hypertension. We determined whether reported SNPs influenced STK39 expression in vivo, or were associated with BP in a large British Caucasian cohort. METHODS: 1372 members of 247 Caucasian families ascertained through a hypertensive proband were genotyped for reported risk variants in STK39 (rs6749447, rs3754777, rs35929607) using Sequenom technology. MERLIN software was used for family-based association testing. Cis-acting influences on expression were assessed in vivo using allelic expression ratios in cDNA from peripheral blood cells in 35 South African individuals heterozygous for a transcribed SNP in STK39 (rs1061471) and quantified by mass spectrometry (Sequenom). RESULTS: No significant association was seen between the SNPs tested and systolic or diastolic BP in clinic or ambulatory measurements (all p > 0.05). The tested SNPs were all associated with allelic expression differences in peripheral blood cells (p < 0.05), with the most significant association for the intronic SNP rs6749447 (P = 9.9 x 10-4). In individuals who were heterozygous for this SNP, on average the G allele showed 13% overexpression compared to the T allele. CONCLUSIONS: STK39 expression is modified by polymorphisms acting in cis and the typed SNPs are associated with allelic expression of this gene, but there is no evidence for an association with BP in a British Caucasian cohort. DA - 2009 DB - OpenUCT DO - 10.1186/1471-2350-10-135 DP - University of Cape Town J1 - BMC Medical Genetics LK - https://open.uct.ac.za PB - University of Cape Town PY - 2009 T1 - STK39 polymorphisms and blood pressure: an association study in British Caucasians and assessment of cis-acting influences on gene expression TI - STK39 polymorphisms and blood pressure: an association study in British Caucasians and assessment of cis-acting influences on gene expression UR - http://hdl.handle.net/11427/14529 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/14529
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2350-10-135
dc.identifier.vancouvercitationCunnington MS, Kay C, Avery P, Mayosi B, Koref M, Keavney B. STK39 polymorphisms and blood pressure: an association study in British Caucasians and assessment of cis-acting influences on gene expression. BMC Medical Genetics. 2009; http://hdl.handle.net/11427/14529.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_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 Licenseen_ZA
dc.rights.holder2009 Cunnington et al; licensee BioMed Central Ltd.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceBMC Medical Geneticsen_ZA
dc.source.urihttp://www.biomedcentral.com/bmcmedgenet/en_ZA
dc.subject.otherHuman Geneticsen_ZA
dc.titleSTK39 polymorphisms and blood pressure: an association study in British Caucasians and assessment of cis-acting influences on gene expressionen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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