Chen Jimmy S, Esko Jeffrey D, Walker Evan, Gordts Philip L S M, Baxter Sally L, Toomey Christopher B
Division of Ophthalmology Informatics and Data Science, Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California San Diego, La Jolla, California.
Glycobiology Research and Training Center, University of California San Diego, La Jolla, California.
Ophthalmology. 2025 Jun;132(6):684-691. doi: 10.1016/j.ophtha.2024.12.039. Epub 2025 Jan 3.
Extracellular lipoprotein aggregation is a critical event in age-related macular degeneration (AMD) pathogenesis. In this study, we sought to analyze associations between clinical and genetic-based factors related to lipoprotein metabolism and risk for AMD in the All of Us research program.
Cross-sectional retrospective data analysis.
A total of 5028 healthy participants and 2328 patients with AMD from All of Us.
Participants with and without AMD were age, race, and sex matched in a 1:2 ratio, respectively. Smoking status, history of hyperlipidemia, and statin use were extracted in a binary manner. Statin use was further subcategorized into hepatically versus nonhepatically metabolized statins. Laboratory values for low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TGs) were also extracted, and outliers were excluded from analysis. The PLINK toolkit was used to extract single nucleotide polymorphisms (SNPs) associated with LDL and HDL dysregulation, as published in prior work. Odds ratio curves were computed to assess the risk between LDL, TG, and HDL versus AMD. All clinical and genetic variables were input into a multivariable logistic regression model, and odds ratios and P values were generated.
Statistical significance of risk factors for AMD, thresholded at P ≤ 0.05.
On multivariable regression analysis, statin use and low and high HDL were significantly associated with increased AMD risk (P < 0.001 for all variables). Additionally, the multivariable regression implicated HDL-associated SNP's increased risk for AMD. Last, LPA was identified (P = 0.007) as a novel SNP associated with increased AMD risk.
There exists a U-shaped relationship between HDL and AMD risk, such that high and low HDL are significantly associated with increased AMD risk. Additionally, SNPs associated with HDL metabolism are associated with AMD risk. This analysis further establishes the role of HDL in AMD pathogenesis.
FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
细胞外脂蛋白聚集是年龄相关性黄斑变性（AMD）发病机制中的关键事件。在本研究中，我们试图在“我们所有人”研究项目中分析脂蛋白代谢相关的临床和遗传因素与AMD风险之间的关联。
横断面回顾性数据分析。
“我们所有人”项目中的5028名健康参与者和2328名AMD患者。
有和没有AMD的参与者分别按1:2的比例进行年龄、种族和性别匹配。吸烟状况、高脂血症病史和他汀类药物使用情况以二元方式提取。他汀类药物使用情况进一步细分为肝代谢和非肝代谢他汀类药物。还提取了低密度脂蛋白（LDL）、高密度脂蛋白（HDL）和甘油三酯（TGs）的实验室值，并将异常值排除在分析之外。如先前工作中所发表的，使用PLINK工具包提取与LDL和HDL失调相关的单核苷酸多态性（SNP）。计算比值比曲线以评估LDL、TG和HDL与AMD之间的风险。所有临床和遗传变量都输入到多变量逻辑回归模型中，并生成比值比和P值。
AMD危险因素的统计学显著性，以P≤0.05为阈值。
在多变量回归分析中，他汀类药物使用以及低HDL和高HDL与AMD风险增加显著相关（所有变量P<0.001）。此外，多变量回归表明与HDL相关的SNP增加了AMD风险。最后，脂蛋白A（LPA）被确定（P = 0.007）为与AMD风险增加相关的新SNP。
HDL与AMD风险之间存在U型关系，即高HDL和低HDL均与AMD风险增加显著相关。此外，与HDL代谢相关的SNP与AMD风险相关。该分析进一步确立了HDL在AMD发病机制中的作用。
在参考文献之后可能会有专有或商业披露。
