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Novel quantitative trait loci for central corneal thickness identified by candidate gene analysis of osteogenesis imperfecta genes
journal contribution
posted on 2023-05-18, 00:42 authored by Dimasi, DP, Chen, JY, Alexander HewittAlexander Hewitt, Klebe, S, Davey, R, Stirling, J, Thompson, E, Forbes, R, Tan, TY, Savarirayan, R, David MackeyDavid Mackey, Healey, PR, Mitchell, P, Kathryn BurdonKathryn Burdon, Craig, JEOsteogenesis 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.
History
Publication title
Human GeneticsVolume
127Pagination
33-44ISSN
0340-6717Department/School
Tasmanian School of MedicinePublisher
Springer-VerlagPlace of publication
175 Fifth Ave, New York, USA, Ny, 10010Rights statement
Copyright 2009 Springer-VerlagRepository Status
- Restricted