Role of plasma fatty acid in age-related macular degeneration: insights from a mendelian randomization analysis.
Lipids Health Dis
; 23(1): 206, 2024 Jun 29.
Article
em En
| MEDLINE
| ID: mdl-38951820
ABSTRACT
BACKGROUND:
An imbalance in lipid metabolism has been linked to the development of AMD, but the causal relationship between AMD and plasma fatty acids (FAs) remains controversial. Using a two-sample Mendelian randomization (MR) approach, we sought to evaluate the impact of specific FA plasma levels on the risk of different AMD subtypes.METHODS:
We analysed genome-wide association data of circulating FAs from 115,006 European-descended individuals in the UK Biobank. These data were used in a two-sample MR framework to assess the potential role of circulating FAs in developing wet and dry AMD. Sensitivity analyses were conducted to ensure the robustness of our findings. Additional multivariable and locus-specific MR analyses were conducted to evaluate direct effects of FA on AMD subtypes, minimizing biases from lipoprotein-related traits and triglycerides.RESULTS:
Mendelian randomization revealed associations of omega-3 was associated with decreased wet (OR 0.78, 95%CI 0.66-0.92) and dry AMD (0.85, 0.74-0.97) risk, showed a protective effect on AMD. Notably, the omega-6 to omega-3 ratio showed potential causal effects on both wet (1.27, 1.03-1.56) and dry AMD (1.18, 1.02-1.37). Multivariable MR suggested that the causal relationship of omega-3, omega-6 to omega-3 ratio on wet AMD persists after conditioning on HDL, LDL and triglycerides, albeit with slightly diminished evidence strength. Locus-specific MR linked to omega-3(FADS1, 0.89, 0.82-0.98; FADS2, 0.88, 0.81-0.96) and omega-6 to omega-3 ratio (FADS1, 1.10, 1.02-1.20; FADS2, 1.11, 1.03-1.20) suggests causal effects of these factors on wet AMD.CONCLUSIONS:
The associations between plasma FA concentrations and AMD, suggest potential causal role of omega-3, and the omega-6 to omega-3 ratio in wet AMD. These results underscore the impact of an imbalanced circulating omega-3 and omega-6 FA ratio on AMD pathophysiology from MR perspective.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos Graxos Ômega-3
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Polimorfismo de Nucleotídeo Único
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Ácidos Graxos Ômega-6
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Estudo de Associação Genômica Ampla
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Análise da Randomização Mendeliana
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Dessaturase de Ácido Graxo Delta-5
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Degeneração Macular
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Lipids Health Dis
Assunto da revista:
BIOQUIMICA
/
METABOLISMO
Ano de publicação:
2024
Tipo de documento:
Article