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

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES iScience Pub Date : 2024-11-08 DOI:10.1016/j.isci.2024.111344

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

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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.

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降脂药物和补体因子 H 基因分型--老年性黄斑变性的个性化治疗策略

我们调查了新加坡眼病流行病学研究（SEED）（5,579 人）和英国生物数据库研究（445,727 人）中的主要补体遗传变异对降脂药物（LLD）对老年性黄斑变性（AMD）的影响是否存在差异。针对每个层的 20 个补体遗传变异，确定了低密度脂蛋白血症的影响。在 SEED 研究中，484 人患上了 AMD，其中 216 人的病情在 6 年内有所发展。rs1061170变体（补体因子H基因）是我们在这两个人群中发现的唯一具有保护作用的变体。在 SEED（几率比 [OR] = 0.41；95% 置信区间 [CI]，0.19-0.87）和 UK Biobank（危险比 [HR] = 0.65；95% 置信区间 [CI]，0.45-0.93）中，至少携带一个 C 等位基因的个体具有这种效应。这些效应分别相当于降低了50%和35%的AMD风险。我们的研究凸显了基于补体基因分型的个性化黄斑变性治疗的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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