June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
SLCO1B1 gene, statin use and incidence of age-related cataract: The Blue Mountains Eye Study
Author Affiliations & Notes
  • Ava Grace Tan
    Centre for Vision Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia
  • Annette Kifley
    Centre for Vision Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia
  • Barbara E K Klein
    Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, United States
  • Kristine E Lee
    Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, United States
  • Sudha K Iyengar
    Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, United States
    Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio, United States
  • Gyungah Jun
    Andover Product Creation Innovation System, Esai Inc., Andover, Massachusetts, United States
  • Elizabeth G Holliday
    Centre for Clinical Epidemiology and Biostatistics, and School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia
  • Rodney J Scott
    Centre for Clinical Epidemiology and Biostatistics, and School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia
    Hunter Medical Research Institute and Hunter Area Pathology Service, Newcastle, New South Wales, Australia
  • Yik Ying Teo
    Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
    Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore
  • Ching-Yu Cheng
    Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
    Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore
  • Tien Yin Wong
    Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore
    Graduate Medical School, Duke-NUS, Singapore, Singapore
  • Robert Cumming
    School of Public Health, The University of Sydney, Sydney, New South Wales, Australia
  • Paul Mitchell
    Centre for Vision Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia
  • Jie Jin Wang
    Centre for Vision Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia
  • Footnotes
    Commercial Relationships   Ava Tan, None; Annette Kifley, None; Barbara Klein, None; Kristine Lee, None; Sudha Iyengar, None; Gyungah Jun, None; Elizabeth Holliday, None; Rodney Scott, None; Yik Teo, None; Ching-Yu Cheng, None; Tien Wong, None; Robert Cumming, None; Paul Mitchell, None; Jie Jin Wang, None
  • Footnotes
    Support  Australian NHMRC grant nos. 974159, 211069, and 1031058 and Australian NHMRC postgraduate research scholarship GNT1094094.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5718. doi:
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      Ava Grace Tan, Annette Kifley, Barbara E K Klein, Kristine E Lee, Sudha K Iyengar, Gyungah Jun, Elizabeth G Holliday, Rodney J Scott, Yik Ying Teo, Ching-Yu Cheng, Tien Yin Wong, Robert Cumming, Paul Mitchell, Jie Jin Wang; SLCO1B1 gene, statin use and incidence of age-related cataract: The Blue Mountains Eye Study. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5718.

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

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Abstract

Purpose : There have been inconsistencies among population-based studies regarding the association of statins with cataract development. While there are numerous genes involved in the statin pathway, polymorphisms of the SLCO1B1 gene have been associated with impaired statin metabolism leading to high statin concentration. We aim to investigate associations between SLCO1B1 polymorphisms, statin use and age-related cataract in a longitudinal population-based study.

Methods : Of the survivors of 3654 participants of the Blue Mountains Eye Study examined at baseline (1992-4), 2334 (75.8%) and 1952 (76.7%) were followed 5 and 10 years later. Eye examinations including lens photography were conducted at each visit. Cataract was graded using the Wisconsin Cataract Grading System. Statin use was self-reported. DNA was extracted from blood samples. Select genotyped SLCO1B1 SNPs (n=10) were assessed for associations with cumulative 5 and 10 year incident cataract. Hazard ratios (HR, 95% CI) were estimated using discrete logistic regression adjusting for age, sex, smoking status, hypertension, diabetes, myopia, inhaled and oral steroids and education level. Gene-environment interactions were examined. Adjustment for multiple testing of SNPs using a correction based on the number of independent tests accounting for LD among SNPs, a p value of .008 was considered statistically significant for multiple testing across 6 SNPs.

Results : Among statin users, incidence of cortical, nuclear and posterior subcapsular cataract was 16.0%, 32.4% and 5.6%, respectively, compared with 23.0%, 29.9%, 7.0% in non-statin users. No SNPs were significantly associated with incidence of any cataract type nor were any significant interactions found between SNPs and statin use. However, the strongest gene-environment interaction was suggested between rs4149013 and statin use for incident cortical cataract (p=.017). Stratified analysis by rs4149013 genotype showed non-significant decreased risk of cortical cataract among statin users with AA genotype (HR 0.44, 95% CI 0.17-1.11, p=.081), but non-significant increased risk among statin users with GA/GG genotype (HR 8.35, 95% CI 1.03-67.44, p=.047).

Conclusions : Our finding suggested a differential effect of statin use on incident cortical cataract by SLCO1B1 genotypes. Investigating effect of other genes involved in the statin pathway are planned. Further studies with larger samples are warranted.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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