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

David Dimasi, Jern Yee Chen, Alex Hewitt, Sonja Klebe, Richard Davey, John Stirling, E Thompson, Robin Forbes, Tiong Tan, Ravi Savarirayan, David Mackey, Paul Healey, Paul Mitchell, Kathryn Burdon, Jamie Craig

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    21 Citations (Scopus)

    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 signiWcantly lower compared to a normal population (P < 0.001). We then investigated CCT and corneal collagen Wbril diameter and density in a mouse model of OI with a col1a2 mutation. Mean CCT was signiWcantly lower in mutant mice (P = 0.002), as was corneal collagen Wbril diameter (P = 0.034), whilst collagen Wbril density was signiWcantly 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 signiWcantly 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 Wrst evidence of quantitative trait loci that inXuence 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 inXuenced by CCT.

    Original languageEnglish
    Pages (from-to)33-44
    Number of pages12
    JournalHuman Genetics
    Volume127
    Issue number1
    DOIs
    Publication statusPublished - Jan 2010

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  • Cite this

    Dimasi, D., Chen, J. Y., Hewitt, A., Klebe, S., Davey, R., Stirling, J., Thompson, E., Forbes, R., Tan, T., Savarirayan, R., Mackey, D., Healey, P., Mitchell, P., Burdon, K., & Craig, J. (2010). Novel quantitative trait loci for central corneal thickness identified by candidate gene analysis of osteogenesis imperfecta genes. Human Genetics, 127(1), 33-44. https://doi.org/10.1007/s00439-009-0729-3