September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Testosterone pathway polymorphisms in relation to primary open angle glaucoma: an analysis stratified by sex
Author Affiliations & Notes
  • Louis R Pasquale
    Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
    Channing Division of Network Medicine, Brigham & Women's Hospital, Boston, Massachusetts, United States
  • Jessica Cooke Bailey
    Case Western Reserve University, Cleveland, Ohio, United States
  • Jae H Kang
    Schepens Eye Research Institute, Boston, Massachusetts, United States
  • Hugo Aschard
    Harvard School of Public Health, Boston, Massachusetts, United States
  • Michael A Hauser
    Duke University Medical School, Durham, North Carolina, United States
  • R Rand Allingham
    Duke University Medical School, Durham, North Carolina, United States
  • David A Sullivan
    Schepens Eye Research Institute, Boston, Massachusetts, United States
  • Jonathan L Haines
    Case Western Reserve University, Cleveland, Ohio, United States
  • Janey L Wiggs
    Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Louis Pasquale, None; Jessica Cooke Bailey, None; Jae Kang, None; Hugo Aschard, None; Michael Hauser, None; R Rand Allingham, None; David Sullivan, None; Jonathan Haines, None; Janey Wiggs, None
  • Footnotes
    Support  NEI R01 EY015473 (LRP); HG005259-01 (JLW); HG004728 (LRP); UO1-HG004424 (Broad)
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 815. doi:
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    • Get Citation

      Louis R Pasquale, Jessica Cooke Bailey, Jae H Kang, Hugo Aschard, Michael A Hauser, R Rand Allingham, David A Sullivan, Jonathan L Haines, Janey L Wiggs; Testosterone pathway polymorphisms in relation to primary open angle glaucoma: an analysis stratified by sex. Invest. Ophthalmol. Vis. Sci. 2016;57(12):815.

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

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Abstract

Purpose : Primary open angle glaucoma (POAG) is a strongly age-related disease and shifting sex hormones are an intregal aspect of the aging process. We assessed the association between a testosterone metabolism single nucleotide polymorphism (SNP) panel in relation to primary open-angle glaucoma (POAG), accounting for gender.

Methods : We included 3,853 POAG cases and 33,495 controls from the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (NEIGHBORHOOD) genotyped on various platforms and imputed to 6,425,680 markers using the 1000 genome reference panel. We assessed the relation between a SNP panel respresentative of testosterone metabolism (2916 SNPs in 16 genes) and POAG using pathway- and gene-based approaches with the Pathway Analysis by Randomization Incorporating Structure (PARIS) software.
PARIS executes 10,000 permutations to assess statistical significance relative to the pathway and genes of comparable genetic architecture. We evaluated POAG overall as well as POAG subtypes defined as known maximum intraocular pressure (IOP) ≥22 mm Hg (high-pressure glaucoma (HPG)) or IOP <22 mmHg (normal pressure glaucoma (NPG) at diagnosis.

Results : In joint analyses of both sexes, the testosterone metabolism SNP panel was not associated with POAG overall (permuted p=0.77) and NPG (p=1.0), but was associated HPG (p<0.0001). Among women this SNP panel was not associated with POAG, NPG or HPG (p≥0.70). Among men, the testosterone SNP pathway was associated with POAG overall (p=0.0001) and HPG (p<0.0001) but not NPG (p=0.98). Gene-based analyses revealed an association between the 17-beta hydroxysteroid dehydrogenase-12 gene (HSD17B12) and HPG in men (p<0.0001) and women (p=0.0002). The figure highlights other genes associated with HTG in men. Interestingly, SNPs in aromatoase (CYP19A1) responsible for converting androstenedione and testosterone to estrone and estradiol, respectively were not assocated with any POAG subtype stratied by sex (p>0.14).

Conclusions : Genetic variants involved in testosterone metabolism play a role in elevated IOP and POAG.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

Testosterone pathway

Testosterone pathway

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