ArticleOphthalmology science2022
Relationships between Lipid-Related Metabolites and Age-Related Macular Degeneration Vary with Complement Genotype.
Article in Ophthalmology science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- Article
- High-Density Lipoprotein Cholesterol Levels and Risk of Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2026Article
- Exploring Therapeutic Targets for Age-Related Macular Degeneration From Circulating Proteins to Plasma Metabolites in the European Population.Translational vision science & technology · 2025Article
- Lipid-lowering drug and complement factor H genotyping-personalized treatment strategy for age-related macular degeneration.iScience · 2024Article
- The Potential Causal Association of Apolipoprotein A and B and Age-Related Macular Degeneration: A Mendelian Randomisation Study.Biomedicines · 2024Article
- Application of mendelian randomization in ocular diseases: a review.Human genomics · 2024Review
- Metabolomics studies in common multifactorial eye disorders: a review of biomarker discovery for age-related macular degeneration, glaucoma, diabetic retinopathy and myopia.Frontiers in molecular biosciences · 2024Review
- Interplay between Lipids and Complement Proteins-How Multiomics Data Integration Can Help Unravel Age-related Macular Degeneration Pathophysiology: A Proof-of-concept Study.Ophthalmology scienceArticle
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Objective: Lipid dysregulation and complement system (CS) activation are 2 important pathophysiology pathways for age-related macular degeneration (AMD). We hypothesized that the relationship between lipids and AMD may also differ according to CS genotype profile. Thus, the objective was to investigate the relationships between lipid-related metabolites and AMD according to CS genotypes. Design: Population-based cross-sectional study. Participants: A total of 6947 participants from Singapore Epidemiology of Eye Diseases study with complete relevant data were included. Methods: We investigated a total of 32 blood lipid-related metabolites from nuclear magnetic resonance metabolomics data including lipoproteins and their subclasses, cholesterols, glycerides, and phospholipids, as well as 4 CS single nucleotide polymorphisms (SNPs): rs10922109 (complement factor H), rs10033900 (complement factor I), rs116503776 (C2-CFB-SKIV2L), and rs2230199 (C3). We first investigated the associations between AMD and the 32 lipid-related metabolites using multivariable logistic regression models. Then, to investigate whether the effect of lipid-related metabolites on AMD differ according to the CS SNPs, we tested the possible interactions between the CS SNPs and the lipid-related metabolites. Main Outcome Measures: Age-related macular degeneration was defined using the Wisconsin grading system. Results: Among the 6947 participants, the prevalence of AMD was 6.1%, and the mean age was 58.3 years. First, higher levels of cholesterol in high-density lipoprotein (HDL) and medium and large HDL particles were associated with an increased risk of AMD, and higher levels of serum total triglycerides (TG) and several very-low-density lipoprotein subclass particles were associated with a decreased risk of AMD. Second, these lipids had significant interaction effects on AMD with 2 CS SNPs: rs2230199 and rs116503776 (after correction for multiple testing). For rs2230199, in individuals without risk allele, higher total cholesterol in HDL2 was associated with an increased AMD risk (odds ratio [OR] per standard deviation increase, 1.20; 95% confidence interval (CI), 1.06-1.37; Conclusions: Lipid-related metabolites exhibit opposite directions of effects on AMD according to CS genotypes. This indicates that lipid metabolism and CS may have synergistic interplay in the AMD pathogenesis.
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