High-density lipoproteins are a known risk factor for cardiovascular disease, and previous research demonstrated an association between cardiovascular disease and age-related macular degeneration. However, research into associations between lipoproteins and age-related macular degeneration is ongoing. To address this need, researchers examined the complex role of lipoproteins, particularly high-density lipoproteins, in age-related macular degeneration pathogenesis.
In a pre-proof, published in Ophthalmology, the researchers noted that the connection between lipoproteins and age-related macular degeneration (AMD) lies in the drusen that characterize the disease. “Characteristics of drusen associated with disease progression include size of drusen, number of drusen, and drusen confluence. Although it is established that drusen contain extracellular lipoprotein aggregates, the class of lipoproteins that compose drusen in AMD progression is not well described,” they wrote.
Both low and high HDL levels were significantly associated with increased AMD risk: OR = 1.28 and OR = 1.28, respectively. However, no significant associations were observed between LDL or triglyceride levels and AMD risk. The findings are consistent with both high and low HDLs being linked to cardiovascular disease, the investigators noted. The lack of association between LDLs and triglycerides and AMD risk “suggests that plasma HDL specifically may play a role in progression to early and intermediate AMD.”
The cross-sectional analysis used data from 7,356 participants (2,328 AMD patients and 5,028 matched controls) in the National Institutes of Health’s All of Us Research Program, and multivariable regression and odds ratio (OR) curves to evaluate associations between high-density lipoprotein (HDL) levels and AMD risk. The data included laboratory values for lipoproteins (HDL, low-density lipoproteins [LDL], and triglycerides), smoking history, and statin use, as well as single nucleotide polymorphisms (SNPs) associated with lipid metabolism. Researchers identified a U-shaped association between HDL levels and AMD risk.
SNPs related to HDL metabolism were also linked to AMD risk. ABCA1 and LIPC showed protective effects (OR = 0.88 and OR = 0.86), but LPA (lipoprotein(a)) emerged as a novel risk factor (OR = 1.37). This SNP may contribute to drusenogenesis along with HDLs, though this association requires further exploration.
Hepatically metabolized statins were associated with a higher AMD risk (OR = 1.36), while non-hepatically metabolized statins did not show significant associations, likely due to data limitations. Smoking history independently increased AMD risk (OR = 1.30).
Genetic components may have many applications,“including discovering novel genetic risk factors, associations with ophthalmic and systemic disease and pathophysiological development, and exploring clinical and genetic differences between populations,” researchers noted. They suggested subgroup analyses of AMD severity in future studies as more data is added to All of Us.
A full list of author disclosures can be found in the published research.
