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Abstract #54468 Published in IGR 15-3
Estrogen pathway polymorphisms in relation to primary open angle glaucoma: an analysis accounting for gender from the United States
Pasquale LR; Loomis SJ; Weinreb RN; Kang JH; Yaspan BL; Bailey JC; Gaasterland D; Gaasterland T; Lee RK; Scott WK; Lichter PR; Budenz DL; Liu Y; Realini T; Friedman DS; McCarty CA; Moroi SE; Olson L; Schuman JS; Singh K; Vollrath D; Wollstein G; Zack DJMolecular Vision 2013; 19: 1471-1481
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.
Department of Ophthalmology, Mass Eye & Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA. Louis_Pasquale@meei.harvard.edu
Classification:
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
1.3 Pathogenesis (Part of: 1 General aspects)
3.6 Cellular biology (Part of: 3 Laboratory methods)
