William Harvey Research Institute, Queen Mary University of London, London, EC1M 6BQ, UK.
Blizard Institute, Queen Mary University of London, London, E1 2AB, UK.
Pharmacogenomics J. 2023 Sep;23(5):134-139. doi: 10.1038/s41397-023-00307-w. Epub 2023 May 23.
Reported association between statin use and cataract risk is controversial. The SLCO1B1 gene encodes a transport protein responsible for statin clearance. The aim of this study was to investigate a possible association between the SLCO1B1*5 reduced function variant and cataract risk in statin users of South Asian ethnicity.
The Genes & Health cohort consists of British-Bangladeshi and British-Pakistani participants from East London, Manchester and Bradford, UK. SLCO1B15 genotype was assessed with the Illumina GSAMD-24v3-0-EA chip. Medication data from primary care health record linkage was used to compare those who had regularly used statins compared to those who had not. Multivariable logistic regression was used to test for association between statin use and cataracts, adjusting for population characteristics and potential confounders in 36,513 participants. Multivariable logistic regression was used to test association between SLCO1B15 heterozygotes or homozygotes and cataracts, in subgroups having been regularly prescribed statins versus not.
Statins were prescribed to 35% (12,704) of participants (average age 41 years old, 45% male). Non-senile cataract was diagnosed in 5% (1686) of participants. An apparent association between statins and non-senile cataract (12% in statin users and 0.8% in non-statin users) was negated by inclusion of confounders. In those prescribed a statin, presence of the SLCO1B1*5 genotype was independently associated with a decreased risk of non-senile cataract (OR 0.7 (CI 0.5-0.9, p 0.007)).
Our findings suggest that there is no independent association between statin use and non-senile cataract risk after adjusting for confounders. Among statin users, the SLCO1B1*5 genotype is associated with a 30% risk reduction of non-senile cataracts. Stratification of on-drug cohorts by validated pharmacogenomic variants is a useful tool to support or repudiate adverse drug events in observational cohorts.
他汀类药物使用与白内障风险之间的关联报道存在争议。SLCO1B1 基因编码一种负责他汀类药物清除的转运蛋白。本研究旨在探讨南亚裔他汀类药物使用者中 SLCO1B1*5 功能降低变异体与白内障风险之间的可能关联。
基因与健康队列包括来自英国伦敦东部、曼彻斯特和布拉德福德的孟加拉裔和巴基斯坦裔参与者。使用 Illumina GSAMD-24v3-0-EA 芯片评估 SLCO1B15 基因型。通过初级保健健康记录链接比较经常使用他汀类药物的患者与未使用的患者的药物数据。在 36513 名参与者中,采用多变量逻辑回归调整人群特征和潜在混杂因素,检验他汀类药物使用与白内障之间的关联。采用多变量逻辑回归检验 SLCO1B15 杂合子或纯合子与白内障之间的关联,在经常开具他汀类药物与未开具他汀类药物的亚组中进行。
35%(12704 人)的参与者被开具了他汀类药物(平均年龄 41 岁,45%为男性)。5%(1686 人)的参与者被诊断为非老年性白内障。他汀类药物与非老年性白内障之间的关联(他汀类药物使用者中为 12%,非他汀类药物使用者中为 0.8%)在纳入混杂因素后被否定。在开具他汀类药物的患者中,SLCO1B1*5 基因型的存在与非老年性白内障风险降低独立相关(OR 0.7(95%CI 0.5-0.9,p<0.007))。
在调整混杂因素后,我们的研究结果表明,他汀类药物使用与非老年性白内障风险之间没有独立关联。在他汀类药物使用者中,SLCO1B1*5 基因型与非老年性白内障风险降低 30%相关。对验证后的药物基因组学变异进行药物队列分层是支持或否定观察性队列中不良药物事件的有用工具。