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TOPLINE:

Both low and high levels of high-density lipoprotein (HDL) are associated with an increased risk for age-related macular degeneration (AMD). This study also identified a potential novel single-nucleotide polymorphism linked to an elevated risk for the retina condition.

METHODOLOGY:

• Researchers conducted a cross-sectional retrospective analysis using data from the All of Us research program to assess the association between lipoprotein and the risk for AMD.
• They analyzed data from 2328 patients with AMD (mean age, 75.5 years; 46.7% women; 84.2% White individuals) and 5028 matched controls (mean age, 75.6 years; 52.5% women; 82.9% White individuals).
• Data were extracted for smoking status, history of hyperlipidemia, use of statins (categorized as hepatically and non-hepatically metabolized), and laboratory values for total triglyceride, low-density lipoprotein (LDL), and HDL levels.
• Data for single-nucleotide polymorphisms associated with the dysregulation of LDL and HDL metabolism were extracted using the PLINK toolkit.

TAKEAWAY:

• Both high and low HDL levels were associated with an increased risk for AMD (adjusted odds ratio [aOR], 1.28 for both; both P < .001), whereas low and high levels of triglyceride and LDL did not demonstrate a statistically significant association with the risk for AMD.
• A history of smoking and statin use showed significant associations with an increased risk for AMD (aOR, 1.30 and 1.36, respectively; both P < .001).
• Single-nucleotide polymorphisms in the genes associated with HDL metabolism, ABCA1 and LIPC, were negatively associated with the risk for AMD (aOR, 0.88; P = .04 and aOR, 0.86; P = .001, respectively).
• Lipoprotein(a) or Lp(a) was identified as a novel single nucleotide polymorphism linked to an increased risk for AMD (aOR, 1.37; P = .007).

IN PRACTICE:

“Despite conflicting evidence regarding the relationship with elevated HDL and AMD risk, this is to our knowledge the first time a U-shaped relationship with low and high HDL and AMD has been described. In fact, the presence of a U-shaped relationship may explain inconsistency in prior analyses comparing mean HDL levels in AMD and control populations,” the authors of the study wrote. 

SOURCE:

The study was led by Jimmy S. Chen, MD, of the Viterbi Family Department of Ophthalmology and Shiley Eye Institute at the University of California, San Diego. It was published online on January 3, 2025, in Ophthalmology.

LIMITATIONS:

The study was limited by the retrospective collection and analysis of data. The use of billing codes for diagnosis extraction may have introduced documentation inaccuracies. The subgroup analysis by severity of AMD was not performed.

DISCLOSURES:

One of the authors was funded by grants from the National Eye Institute (NEI), Research to Prevent Blindness Career Development Award, Robert Machemer MD and International Retinal Research Foundation, and the UC San Diego Academic Senate. Another author reported receiving a grant from the National Heart, Lung, and Blood Institute, while a third author received funding from the National Institutes of Health (NIH), NEI, and Research to Prevent Blindness. The All of Us Research Program was supported by grants from the NIH and other sources. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.