Estrogen pathway polymorphisms in relation to primary open angle glaucoma: an analysis accounting for gender from the United States

Mol Vis. 2013 Jul 12;19:1471-81. Print 2013.

Abstract

Purpose: Circulating estrogen levels are relevant in glaucoma phenotypic traits. We assessed the association between an estrogen metabolism single nucleotide polymorphism (SNP) panel in relation to primary open angle glaucoma (POAG), accounting for gender.

Methods: We included 3,108 POAG cases and 3,430 controls of both genders from the Glaucoma Genes and Environment (GLAUGEN) study and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium genotyped on the Illumina 660W-Quad platform. We assessed the relation between the SNP panels representative of estrogen metabolism and POAG using pathway- and gene-based approaches with the Pathway Analysis by Randomization Incorporating Structure (PARIS) software. PARIS executes a permutation algorithm to assess statistical significance relative to the pathways and genes of comparable genetic architecture. These analyses were performed using the meta-analyzed results from the GLAUGEN and NEIGHBOR data sets. We evaluated POAG overall as well as two subtypes of POAG defined as intraocular pressure (IOP) ≥22 mmHg (high-pressure glaucoma [HPG]) or IOP <22 mmHg (normal pressure glaucoma [NPG]) at diagnosis. We conducted these analyses for each gender separately and then jointly in men and women.

Results: Among women, the estrogen SNP pathway was associated with POAG overall (permuted p=0.006) and HPG (permuted p<0.001) but not NPG (permuted p=0.09). Interestingly, there was no relation between the estrogen SNP pathway and POAG when men were considered alone (permuted p>0.99). Among women, gene-based analyses revealed that the catechol-O-methyltransferase gene showed strong associations with HTG (permuted gene p≤0.001) and NPG (permuted gene p=0.01).

Conclusions: The estrogen SNP pathway was associated with POAG among women.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Estrogens / metabolism*
  • Female
  • Genetic Predisposition to Disease*
  • Glaucoma, Open-Angle / diagnosis
  • Glaucoma, Open-Angle / genetics*
  • Glaucoma, Open-Angle / physiopathology
  • Humans
  • Intraocular Pressure
  • Male
  • Metabolic Networks and Pathways / genetics
  • Polymorphism, Single Nucleotide / genetics*
  • Sex Characteristics*
  • Signal Transduction / genetics*
  • United States

Substances

  • Estrogens

Grant support