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dc.contributor.authorKuot, A
dc.contributor.authorHewitt, AW
dc.contributor.authorGriggs, K
dc.contributor.authorKlebe, S
dc.contributor.authorMills, R
dc.contributor.authorJhanji, V
dc.contributor.authorCraig, JE
dc.contributor.authorSharma, S
dc.contributor.authorBurdon, KP
dc.identifierpii: ejhg2011248
dc.identifier.citationKuot, A., Hewitt, A. W., Griggs, K., Klebe, S., Mills, R., Jhanji, V., Craig, J. E., Sharma, S. & Burdon, K. P. (2012). Association of TCF4 and CLU polymorphisms with Fuchs' endothelial dystrophy and implication of CLU and TGFBI proteins in the disease process. EUROPEAN JOURNAL OF HUMAN GENETICS, 20 (6), pp.632-638.
dc.descriptionC1 - Journal Articles Refereed
dc.description.abstractFuchs' endothelial dystrophy (FED) is a disease affecting the corneal endothelium. Recent studies reported significant association of polymorphisms in the TCF4 (transcription factor 4) gene, and a borderline association of PTPRG (protein tyrosine phosphatase, receptor type, G) variants with late-onset FED in Caucasians from the United States. Association of TCF4 has also been reported in the Chinese population. We aimed to determine association of the reported polymorphisms in TCF4 and PTPRG, and association of polymorphisms in the candidate genes ZEB1 (zinc-finger E-box binding homoebox 1), COL8A2 (collagen, type VIII, alpha 2), TGFBI (transforming growth factor, β-induced) and CLU (clusterin) in Australian cases. We also compared the expression of TGFBI and CLU proteins between FED and normal whole corneas. In all, 30 single-nucleotide polymorphisms (SNPs) from the candidate genes were genotyped in 103 cases and 275 controls. Each SNP and haplotype was assessed for association with the disease. SNP analysis identified an association of TCF4 (rs613872 (P=5.25 × 10(-15), OR=4.05), rs9954153 (P=3.37 × 10(-7), OR=2.58), rs2286812 (P=4.23 × 10(-6), OR=2.55) and rs17595731 (P=3.57 × 10(-5), OR=3.79)), CLU (rs17466684; P=0.003, OR=1.85) and one haplotype of TGFBI SNPs (P=0.011, OR=2.29) with FED in Caucasian Australians. No evidence for genetic association of PTPRG, ZEB1 and COL8A2 was found. Immunohistochemistry showed differential expression of CLU and TGFBI proteins in FED-affected compared with normal corneas. In conclusion, variation in TCF4, CLU and TGFBI, but not PTPRG, ZEB1 and COL8A2 genes are associated with FED in Caucasian Australian cases. Differential expression of CLU and TGFBI proteins in FED-affected corneas provides novel insights into the disease mechanism.
dc.subjectQuantitative Genetics (incl. Disease and Trait Mapping Genetics); Ophthalmology; Hearing
dc.subjectSpeech and Their Disorders
dc.titleAssociation of TCF4 and CLU polymorphisms with Fuchs' endothelial dystrophy and implication of CLU and TGFBI proteins in the disease process
dc.typeJournal Article
melbourne.peerreviewPeer Reviewed
melbourne.affiliationThe University of Melbourne
melbourne.affiliation.departmentOphthalmology Eye And Ear Hospital
melbourne.source.titleEuropean Journal of Human Genetics
melbourne.contributor.authorHewitt, Alexander
melbourne.contributor.authorJhanji, Vishal
melbourne.fieldofresearch321201 Ophthalmology
melbourne.seocode200199 Clinical health not elsewhere classified
melbourne.accessrightsAccess this item via the Open Access location

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