Photo Credit: Natali_Mis

The following is a summary of “High Density Lipoproteins Associate with Age-Related Macular Degeneration in the All of Us Research Program,” published in the January 2025 issue of Ophthalmology by Chen et al. 

Researchers conducted a retrospective study to analyze the associations between clinical and genetic factors related to lipoprotein metabolism and the risk for age-related macular degeneration (AMD) in the All of Us research program.  

They matched participants with and without AMD by age, race, and gender in a 1:2 ratio. Smoking status, hyperlipidemia history, and statin use were extracted as binary variables. Statin use was classified into hepatically vs non-hepatically metabolized types. Laboratory values for low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG) were extracted, with outliers excluded. The PLINK toolkit was used to extract single-nucleotide polymorphisms (SNPs) linked to LDL and HDL dysregulation. Odds ratio curves were computed for LDL, TG, and HDL vs AMD risk. All clinical and genetic data were input into a multivariable logistic regression model, generating odds ratios and P -values.  

The results showed the statin use, as well as low and high HDL, were significantly associated with increased AMD risk (P <0.001, <0.001, 0.004, <0.001, respectively). Additionally, multivariable regression analysis indicated that HDL-associated SNPs contributed to increased AMD risk. Furthermore, lipoprotein(a) [LPA] was identified as a novel SNP linked to higher AMD risk (P = 0.007).  

Investigators concluded the U-shaped relationship exists between HDL cholesterol levels and AMD risk, with both high and low HDL levels associated with increased AMD incidence, and that SNPs associated with HDL metabolism further supported a significant role for HDL in the pathogenesis of AMD. 

Source: aaojournal.org/article/S0161-6420(25)00002-8/abstract