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

doi:10.1016/j.isci.2024.111344

Lipid-lowering drug and complement factor H genotyping-personalized treatment strategy for age-related macular degeneration

iScience. 2024 Nov 8;27(12):111344. doi: 10.1016/j.isci.2024.111344. eCollection 2024 Dec 20.

Authors

Can Can Xue¹, Kelvin Y C Teo^{1

2}, Yih Chung Tham^{1

2

3

4}, Hengtong Li^{3

4}, Sahil Thakur¹, Charumathi Sabanayagam^{1

2}, Qiao Fan^{2

5}, David L Silver⁶, Xiaomeng Wang^{1

2

7}, Chui Ming Gemmy Cheung^{1

2}, Tien Yin Wong^{1

2

8}, Usha Chakravarthy⁹, Ching-Yu Cheng^{1

2

3

4}, Simon Nusinovici^{1

2}

Affiliations

¹ Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 169856, Singapore.
² Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore 169857, Singapore.
³ Centre for Innovation & Precision Eye Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
⁴ Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
⁵ Center for Quantitative Medicine, Duke-NUS Medical School, Singapore 169857, Singapore.
⁶ Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore 169857, Singapore.
⁷ Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A∗STAR), Singapore 138673, Singapore.
⁸ Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 100084, China.
⁹ Queen's University of Belfast, Belfast BT7 1NN, UK.

Abstract

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.

Keywords: Cardiovascular medicine; Health sciences; Internal medicine; Medical specialty; Medicine; Pharmacology.