SLCO1B1 gene, statin use and incidence of age-related cataract: The Blue Mountains Eye Study

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.