May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
An Investigation of the Developmental Glaucoma Genes as Genetic Risk Factors in Ocular Hypertension and Primary Open Angle Glaucoma
Author Affiliations & Notes
  • S. Park
    Developmental Biology Unit, UCL Institute of Child Health, London, United Kingdom
  • Y. Jamshidi
    Division of Clinical Developmental Sciences, St George’s Hospital Medical School, London, United Kingdom
  • D. Vaideanu
    Ophthalmology, The Newcastle upon Tyne Hospitals NHS Trust, Newcastle, United Kingdom
  • S. Fraser
    Ophthalmology, Sunderland Eye Infirmary, Sunderland, United Kingdom
  • J. C. Sowden
    Developmental Biology Unit, UCL Institute of Child Health, London, United Kingdom
  • Footnotes
    Commercial Relationships  S. Park, None; Y. Jamshidi, None; D. Vaideanu, None; S. Fraser, None; J.C. Sowden, None.
  • Footnotes
    Support  The Royal College of Surgeons of Edinburgh, Alcon Laboratories
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5125. doi:https://doi.org/
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      S. Park, Y. Jamshidi, D. Vaideanu, S. Fraser, J. C. Sowden; An Investigation of the Developmental Glaucoma Genes as Genetic Risk Factors in Ocular Hypertension and Primary Open Angle Glaucoma. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5125. doi: https://doi.org/.

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

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Abstract

Purpose: : This study aims to ascertain whether alleles of FOXC1, LMX1B, TGFβ2 and BMP4 predispose to ocular hypertension (OHT) and primary open angle glaucoma (POAG) in white British subjects.

Methods: : Two independent cohorts comprised of 332 cases affected with either OHT (n= 57) or POAG (n=275) and 276 matched controls of white British descent were recruited in this study. The candidate genes were screened using 4 tagging single nucleotide polymorphisms (tSNPs) for FOXC1, 5 tSNPs forBMP4, 21 tSNPs forTGFβ2 and 25 tSNPs for LMX1B.

Results: : A significant association was found between a non-coding tSNP situated within intron 2 of LMX1B and POAG cases, for both allele frequency [76.6% of cases vs 68.2% of controls, Χ2= 9.4, fisher's p = 0.002, odds ratio= 1.5 (95% confidence interval = 1.16-2.00)] and genotype frequency (Χ2 = 9.3, fisher's p = 0.009). This association became marginally stronger when combining OHT subjects with POAG cases (OHT-POAG), for both allele frequency [Χ2= 10.9, fisher's p = 0.001, odds ratio= 1.51 (95% confidence interval = 1.19-2.00)] and genotype frequency (Χ2 = 11.1, fisher's p = 0.004). OHT cases by themselves showed an association with the intronic tSNP (Χ2 = 3.9, p =0.0482). More importantly, a 3-tSNP haplotype (ATG) was significantly associated with POAG cases (p = 0.0017, permutation p value = 0.0445), and more so with the combined OHT-POAG cases (p = 0.0007, permutation p value = 0.0206). Variants of FOXC1, TGFβ2 and BMP4 were not associated with either OHT or POAG cases.

Conclusions: : This is the first study to show an association between sequence variants of LMX1B and OHT/POAG. These data suggest that anterior segment dysfunction and/or developmental abnormalities in anterior segment structures caused by altered LMX1B function may predispose to glaucoma in the general adult population. This study provides a platform for further investigation of LMX1B as a genetic risk factor for adult-onset glaucoma.

Keywords: genetics • anterior segment • intraocular pressure 
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