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降脂药物与补体因子H基因分型——年龄相关性黄斑变性的个性化治疗策略

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

作者信息

Xue Can Can, Teo Kelvin Y C, Tham Yih Chung, Li Hengtong, Thakur Sahil, Sabanayagam Charumathi, Fan Qiao, Silver David L, Wang Xiaomeng, Cheung Chui Ming Gemmy, Wong Tien Yin, Chakravarthy Usha, Cheng Ching-Yu, Nusinovici Simon

机构信息

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.

出版信息

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

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) ( = 5,579) and UK Biobank studies ( = 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.

摘要

我们调查了在新加坡眼病流行病学研究(SEED,n = 5579)和英国生物银行研究(n = 445727)中,降脂药物(LLDs)对年龄相关性黄斑变性(AMD)的影响是否因主要补体基因变异而异。针对20种补体基因变异的每个分层确定了LLD的效果。在SEED研究中,484人发生了AMD,216人在6年中病情出现进展。在英国生物银行研究中,913名参与者在11年中发生了AMD。rs1061170变异(补体因子H基因)是我们在两个人群中均发现具有保护作用的唯一变异。在SEED研究中,携带至少一个C等位基因的个体中发现了这种作用(优势比[OR]=0.41;95%置信区间[CI],0.19 - 0.87),在英国生物银行研究中,携带两个C等位基因的个体中也发现了这种作用(风险比[HR]=0.65;95%CI,0.45 - 0.93)。这些作用分别对应AMD风险降低50%和35%。我们的研究突出了基于补体基因分型对AMD进行个性化治疗的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3615/11618023/e64bd047afa1/fx1.jpg

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