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

    Research output: Contribution to journalArticlepeer-review

    24 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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