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Novel quantitative trait loci for central corneal thickness identified by candidate gene analysis of osteogenesis imperfecta genes


Dimasi, DP and Chen, JY and Hewitt, AW and Klebe, S and Davey, R and Stirling, J and Thompson, E and Forbes, R and Tan, TY and Savarirayan, R and Mackey, DA and Healey, PR and Mitchell, P and Burdon, KP and Craig, JE, Novel quantitative trait loci for central corneal thickness identified by candidate gene analysis of osteogenesis imperfecta genes, Human Genetics, 127, (1) pp. 33-44. ISSN 0340-6717 (2010) [Refereed Article]

Copyright Statement

Copyright 2009 Springer-Verlag

DOI: doi:10.1007/s00439-009-0729-3


Osteogenesis imperfecta (OI) is a rare connective tissue disorder caused by mutations in the type I collagen genes, COL1A1 and COL1A2, and is characterised by low bone mass and bone fragility. In this study, we explored the relationship between type 1 collagen genes and the quantitative trait central corneal thickness (CCT). CCT was measured in a cohort of 28 Australian type I OI patients and mean CCT was found to be significantly lower compared to a normal population (P < 0.001). We then investigated CCT and corneal collagen fibril diameter and density in a mouse model of OI with a col1a2 mutation. Mean CCT was significantly lower in mutant mice (P = 0.002), as was corneal collagen fibril diameter (P = 0.034), whilst collagen fibril density was significantly greater in mutants (P = 0.034). Finally, we conducted a genetic study to determine whether common single nucleotide polymorphisms (SNPs) in COL1A1 and COL1A2 are associated with CCT variation in the normal human population. Polymorphism rs2696297 (P = 0.003) in COL1A1 and a three SNP haplotype in COL1A2 (P = 0.007) were all significantly associated with normal CCT variation. These data implicate type 1 collagen in the determination of CCT in both OI patients and normal individuals. This provides the first evidence of quantitative trait loci that influence CCT in a normal population and has potential implications for investigating genes involved in glaucoma pathogenesis, a common eye disease in which the severity and progression is influenced by CCT.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Ophthalmology and Optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Hearing, Vision, Speech and Their Disorders
Author:Hewitt, AW (Professor Alex Hewitt)
Author:Mackey, DA (Professor David Mackey)
Author:Burdon, KP (Associate Professor Kathryn Burdon)
ID Code:91362
Year Published:2010
Web of Science® Times Cited:18
Deposited By:Menzies Institute for Medical Research
Deposited On:2014-05-15
Last Modified:2014-12-17

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