July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Pharmacogenetic markers predictors of response to treatment for primary open angle glaucoma: Systematic review and meta-analysis
Author Affiliations & Notes
  • David Jimenez-Collado
    Escuela de Medicina, Universidad Panamericana, Mexico City, Benito Juárez, Mexico
  • Andric Christopher Perez-Ortiz
    School of Public Health, Yale University, New Haven, Connecticut, United States
    Escuela de Medicina, Universidad Panamericana, Mexico City, Benito Juárez, Mexico
  • Alvaro Rendon
    Institut de la Vision, Paris, France
  • Claudia Zepeda-Palacio
    Fundacion Hospital Nuestra Señora de la Luz IAP, Mexico City, Mexico
    Escuela de Medicina, Universidad Panamericana, Mexico City, Benito Juárez, Mexico
  • Claudia Palacio-Pastrana
    Fundacion Hospital Nuestra Señora de la Luz IAP, Mexico City, Mexico
  • Salvador Jimenez-Chaidez
    Escuela de Medicina, Universidad Panamericana, Mexico City, Benito Juárez, Mexico
  • Bani Antonio-Aguirre
    Escuela de Medicina, Universidad Panamericana, Mexico City, Benito Juárez, Mexico
  • Francisco Javier Estrada-Mena
    Escuela de Medicina, Universidad Panamericana, Mexico City, Benito Juárez, Mexico
  • Footnotes
    Commercial Relationships   David Jimenez-Collado, None; Andric Perez-Ortiz, None; Alvaro Rendon, None; Claudia Zepeda-Palacio, None; Claudia Palacio-Pastrana, None; Salvador Jimenez-Chaidez, None; Bani Antonio-Aguirre, None; Francisco Estrada-Mena, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5151. doi:
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      David Jimenez-Collado, Andric Christopher Perez-Ortiz, Alvaro Rendon, Claudia Zepeda-Palacio, Claudia Palacio-Pastrana, Salvador Jimenez-Chaidez, Bani Antonio-Aguirre, Francisco Javier Estrada-Mena; Pharmacogenetic markers predictors of response to treatment for primary open angle glaucoma: Systematic review and meta-analysis. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5151.

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

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Abstract

Purpose : Intraocular pressure (IOP)-lowering drugs are the first line of treatment for primary open-angle glaucoma (POAG). However, their effect on IOP varies among cases, leading to clinically meaningful variable response rates. This variability is thought to be partly mediated by genetic biomarkers. We aimed to test the effect of pharmacogenetic markers in several genes (identified through a systematic review) on treatment response to IOP-lowering drugs among POAG cases by meta-analysis.

Methods : We conducted a systematic search in MEDLINE, HuGENET, and LILACS databases. We included observational studies that determined genotype based on validated genotyping instruments and with a stringent quality check (e.g. genotyping call rate ≥ 95%, HWE in controls). We collected mean and standard deviation of the percent IOP reduction (%ΔIOP) or mean intraocular pressure among responders and non-responders to IOP-lowering groups based on genotype information. We performed a meta-analysis of these measurements using random and fixed effects models.

Results : There were 125 records from MEDLINE (n = 97), HuGENET (n = 24), and additional sources such as citation alerts, reference mining, unpublished data, etc. (n = 4). We screened 100 titles and abstracts and retrieved 17 records for qualitative and quantitative analyses. The genes consistently reported in the literature by order of frequency were: PTGFR, ADRB2, CYP2D6, SLCO2A1, among others (individual reports). Only three drugs are studied: latanoprost, timolol, and betaxolol. As an example, we displayed the results for PTGFR gene with 3 SNPs [rs3766355, rs12093097, rs3753380] (Figure). In subgroup analyses by population, minor allele (SNP) carriers have significantly greater decreases in IOP after treatment with latanoprost 0.005% [p<0.05] (Figure). The rest of biomarkers in the other genes follow similar trends.

Conclusions : SNPs in several genes are associated with a differential treatment response across ethnicities. As an example, minor allele carriers (AA) from Japanese or Chinese ascent have a favorable response to latanoprost compared to other genotypes (CC, CA). These findings warrant future research towards building individualized precision medicine for POAG incident cases in whom the response to treatment would like to be as accurate and fast as possible.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

Subgroup meta-analysis by ethnicity of rs3766355 in the PTGFR gene.

Subgroup meta-analysis by ethnicity of rs3766355 in the PTGFR gene.

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