Lipid-lowering drug and complement factor H genotyping–personalized treatment strategy for age-related macular degeneration
Can Can Xue,
Kelvin Y.C. Teo,
Yih Chung Tham,
Hengtong Li,
Sahil Thakur,
Charumathi Sabanayagam,
Qiao Fan,
David L. Silver,
Xiaomeng Wang,
Chui Ming Gemmy Cheung,
Tien Yin Wong,
Usha Chakravarthy,
Ching-Yu Cheng,
Simon Nusinovici
Affiliations
Can Can Xue
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 169856, Singapore
Kelvin Y.C. Teo
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 169856, Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore 169857, Singapore
Yih Chung Tham
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 169856, Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore 169857, Singapore; Centre for Innovation & Precision Eye Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
Hengtong Li
Centre for Innovation & Precision Eye Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
Sahil Thakur
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 169856, Singapore
Charumathi Sabanayagam
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 169856, Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore 169857, Singapore
Qiao Fan
Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore 169857, Singapore; Center for Quantitative Medicine, Duke-NUS Medical School, Singapore 169857, Singapore
David L. Silver
Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore 169857, Singapore
Xiaomeng Wang
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 169856, Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore 169857, Singapore; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A∗STAR), Singapore 138673, Singapore
Chui Ming Gemmy Cheung
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 169856, Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore 169857, Singapore
Tien Yin Wong
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 169856, Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore 169857, Singapore; Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 100084, China
Usha Chakravarthy
Queen’s University of Belfast, Belfast BT7 1NN, UK
Ching-Yu Cheng
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 169856, Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore 169857, Singapore; Centre for Innovation & Precision Eye Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
Simon Nusinovici
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 169856, Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore 169857, Singapore; Corresponding author
Summary: We investigated whether the effect of lipid-lowering drugs (LLDs) on age-related macular degeneration (AMD) differs according to the main complement genetic variants in Singapore Epidemiology of Eye Diseases (SEED) (n = 5,579) and UK Biobank studies (n = 445,727). The effect of LLD was determined for each stratum of 20 complement genetic variants. In SEED, 484 individuals developed AMD and 216 showed progression over 6 years. In the UK Biobank, 913 participants developed AMD over 11 years. rs1061170 variant (complement factor H gene) was the only variant for which we found a protective effect in both populations. This effect was found in individuals carrying at least one C allele in SEED (odds ratio [OR] = 0.41; 95% confidence interval [CI], 0.19–0.87) and in individuals carrying two C alleles in UK Biobank (hazard ratio [HR] = 0.65; 95% CI, 0.45–0.93). These effects corresponded to a 50% and 35% decrease in AMD risk, respectively. Our study highlights the potential for personalized therapy for AMD based on complement genotyping.