eCite Digital Repository
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 |
| UTAS Author: | Hewitt, AW (Professor Alex Hewitt) |
| UTAS Author: | Mackey, DA (Professor David Mackey) |
| UTAS Author: | Burdon, KP (Professor Kathryn Burdon) |
| ID Code: | 91362 |
| Year Published: | 2010 |
| Web of Science® Times Cited: | 21 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2014-05-15 |
| Last Modified: | 2014-12-17 |
| Downloads: | 0 |
Repository Staff Only: item control page