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Novel quantitative trait loci for central corneal thickness identified by candidate gene analysis of osteogenesis imperfecta genes
Citation
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
Abstract
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: | 19 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2014-05-15 |
| Last Modified: | 2014-12-17 |
| Downloads: | 0 |
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