Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/16620
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dc.contributor.authorPatel, Sheila K-
dc.contributor.authorWai, Bryan-
dc.contributor.authorLang, Chim C-
dc.contributor.authorLevin, Daniel-
dc.contributor.authorPalmer, Colin NA-
dc.contributor.authorParry, Helen M-
dc.contributor.authorVelkoska, Elena-
dc.contributor.authorHarrap, Stephen B-
dc.contributor.authorSrivastava, Piyush M-
dc.contributor.authorBurrell, Louise M-
dc.date2017-03-30-
dc.date.accessioned2017-04-24T00:38:57Z-
dc.date.available2017-04-24T00:38:57Z-
dc.date.issued2017-04-
dc.identifier.citationEBioMedicine 2017; 18: 171-178en_US
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/16620-
dc.description.abstractLeft ventricular (LV) hypertrophy (LVH) is a heritable trait that is common in type 2 diabetes and is associated with the development of heart failure. The transcriptional factor Kruppel like factor 15 (KLF15) is expressed in the heart and acts as a repressor of cardiac hypertrophy in experimental models. This study investigated if KLF15 gene variants were associated with LVH in type 2 diabetes. In stage 1 of a 2-stage approach, patients with type 2 diabetes and no known cardiac disease were prospectively recruited for a transthoracic echocardiographic assessment (Melbourne Diabetes Heart Cohort) (n=318) and genotyping of two KLF15 single nucleotide polymorphisms (SNPs) (rs9838915, rs6796325). In stage 2, the association of KLF15 SNPs with LVH was investigated in the Genetics of Diabetes Audit and Research in Tayside Scotland (Go-DARTS) type 2 diabetes cohort (n=5631). The KLF15 SNP rs9838915 A allele was associated in a dominant manner with LV mass before (P=0.003) and after (P=0.001) adjustment for age, gender, body mass index (BMI) and hypertension, and with adjusted septal (P<0.0001) and posterior (P=0.004) wall thickness. LVH was present in 35% of patients. Over a median follow up of 5.6years, there were 22 (7%) first heart failure hospitalizations. The adjusted risk of heart failure hospitalization was 5.5-fold greater in those with LVH and the rs9838915 A allele compared to those without LVH and the GG genotype (hazard ratio (HR) 5.5 (1.6-18.6), P=0.006). The association of rs9838915 A allele with LVH was replicated in the Go-DARTS cohort. We have identified the KLF15 SNP rs9838915 A allele as a marker of LVH in patients with type 2 diabetes, and replicated these findings in a large independent cohort. Studies are needed to characterize the functional importance of these results, and to determine if the SNP rs9838915 A allele is associated with LVH in other high risk patient cohorts.en_US
dc.subjectEchocardiogramen_US
dc.subjectGenetic association studyen_US
dc.subjectHeart failureen_US
dc.subjectKruppel like factor 15en_US
dc.subjectLeft ventricular hypertrophyen_US
dc.subjectType 2 diabetesen_US
dc.titleGenetic variation in Kruppel like factor 15 is associated with left ventricular hypertrophy in patients with type 2 diabetes: discovery and replication cohortsen_US
dc.typeJournal Articleen_US
dc.identifier.journaltitleEBioMedicineen_US
dc.identifier.affiliationMedicine (University of Melbourne)en_US
dc.identifier.affiliationCardiologyen_US
dc.identifier.affiliationDivision of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UKen_US
dc.identifier.affiliationPat McPherson Centre for Pharmacogenomics and Pharmacogenetics, Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UKen_US
dc.identifier.affiliationDepartment of Physiology, University of Melbourne, Victoria, Australiaen_US
dc.identifier.pubmedurihttps://pubmed.ncbi.nlm.nih.gov/28400202en_US
dc.identifier.doi10.1016/j.ebiom.2017.03.036en_US
dc.type.contentTexten_US
dc.identifier.orcid0000-0003-1863-7539en_US
dc.type.austinJournal Articleen_US
local.name.researcherBurrell, Louise M
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.openairetypeJournal Article-
crisitem.author.deptMedicine (University of Melbourne)-
crisitem.author.deptMedicine (University of Melbourne)-
crisitem.author.deptCardiology-
crisitem.author.deptGeneral Medicine-
crisitem.author.deptMedicine (University of Melbourne)-
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