May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Contribution of the CBS Gene to Pseudoexfoliation Glaucoma and Interaction With LOXL1
Author Affiliations & Notes
  • B. Fan
    Dept of Ophthalmology - Harvard Med Sch, Mass Eye & Ear Infirmary, Boston, Massachusetts
  • L. R. Pasquale
    Dept of Ophthalmology - Harvard Med Sch, Mass Eye & Ear Infirmary, Boston, Massachusetts
  • C. L. Grosskreutz
    Dept of Ophthalmology - Harvard Med Sch, Mass Eye & Ear Infirmary, Boston, Massachusetts
  • T. Chen
    Dept of Ophthalmology - Harvard Med Sch, Mass Eye & Ear Infirmary, Boston, Massachusetts
  • D. Rhee
    Dept of Ophthalmology - Harvard Med Sch, Mass Eye & Ear Infirmary, Boston, Massachusetts
  • E. A. DelBono
    Dept of Ophthalmology - Harvard Med Sch, Mass Eye & Ear Infirmary, Boston, Massachusetts
  • J. L. Haines
    Center for Human Genetics Research, Vanderbilt School of Medicine, Nashville, Tennessee
  • J. L. Wiggs
    Dept of Ophthalmology - Harvard Med Sch, Mass Eye & Ear Infirmary, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  B. Fan, None; L.R. Pasquale, None; C.L. Grosskreutz, None; T. Chen, None; D. Rhee, None; E.A. DelBono, None; J.L. Haines, None; J.L. Wiggs, None.
  • Footnotes
    Support  National Eye Institute Grants R01 EY013882 and P30 EY014104
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1721. doi:https://doi.org/
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      B. Fan, L. R. Pasquale, C. L. Grosskreutz, T. Chen, D. Rhee, E. A. DelBono, J. L. Haines, J. L. Wiggs; Contribution of the CBS Gene to Pseudoexfoliation Glaucoma and Interaction With LOXL1. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1721. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Pseudoexfoliation syndrome (PXF) and primary open-angle glaucoma (POAG) are two major causes of glaucoma. Recently, a genome-wide association study identified a strong association of the LOXL1 gene with PXF in patients from Iceland and Sweden. This association has been replicated in our study of U.S. clinic-based population with broad ethnic diversity and other studies in Caucasian populations. However, the risk haplotype of LOXL1 is also prevalent in control samples. It indicates additional genetic factors and/or environmental exposures could be involved in the development of this complex disease. In the present study, we investigated LOXL1 and an additional 9 genes that are potential candidates for PXF based on biological and functional data in a case-control sample.

Methods: : A total of 17 SNPs in 10 genes (CBS, DPP10, ELN, LOXL1, LOXL3, MTHFD1, MTHFR, MTR, MTRR and TRIM62) were genotyped in a sample of 206 PXF, 325 POAG and 88 controls. Single-SNP association was analyzed using a chi-squared test. Pairwise-SNP interaction analysis was performed using PLINK. Multiple comparisons were corrected by the Bonferroni method.

Results: : Two non-synonymous SNPs (rs3825942, G153D; rs1048661, R141L) and an intronic SNP (rs2165241) in LOXL1 were significantly associated with PXF (p = 4.9×10-17, 0.003, 4.4×10-12, respectively) but not with POAG (p > 0.31). Two coding SNPs (rs1801181, A360A; rs5742905, I278T) in CBS demonstrated a strong association with PXF (p = 2.2×10-6 and 0.007 respectively) and with POAG (p = 0.006 and 0.02 respectively). Intriguingly, two LOXL1 SNPs (rs2165241 and rs1048661) showed an interactive effect on PXF with a CBS SNP (rs1801181) (p = 0.0049 and 0.046 respectively). Meanwhile, rs1801181 significantly interacted with a MTHFD1 SNP (rs2236225) (p = 0.01) in contributions to PXF development.

Conclusions: : We have identified two new genes (CBS and MTHFD1) that might contribute to PXF interactively with LOXL1. Interestingly, both of these genes function in the regulation of homocysteine metabolism, another factor that has been implicated in PXF. Further functional studies and replication studies are needed to confirm our findings.

Keywords: genetics • candidate gene analysis 
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