PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: Population-based cross-sectional study.
UNASSIGNED: A total of 6947 participants from Singapore Epidemiology of Eye Diseases study with complete relevant data were included.
UNASSIGNED: 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.
UNASSIGNED: Age-related macular degeneration was defined using the Wisconsin grading system.
UNASSIGNED: 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; P = 0.005), whereas, in individuals with at least 1 risk allele, higher levels of these particles were associated with a decreased AMD risk (OR, 0.69; 95% CI, 0.45-1.05; P = 0.079). Conversely, for rs116503776, in individuals without risk allele, higher serum total TG were associated with a decreased AMD risk (OR, 0.84; 95% CI, 0.74-0.95; P = 0.005), whereas, in individuals with 2 risk alleles, higher levels of these particles were associated with an increased risk of AMD (OR, 2.3, 95% CI, 0.99-5.39, P = 0.054).
UNASSIGNED: 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.
UNASSIGNED: Population-based cross-sectional study.
UNASSIGNED: A total of 6947 participants from Singapore Epidemiology of Eye Diseases study with complete relevant data were included.
UNASSIGNED: 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.
UNASSIGNED: Age-related macular degeneration was defined using the Wisconsin grading system.
UNASSIGNED: 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; P = 0.005), whereas, in individuals with at least 1 risk allele, higher levels of these particles were associated with a decreased AMD risk (OR, 0.69; 95% CI, 0.45-1.05; P = 0.079). Conversely, for rs116503776, in individuals without risk allele, higher serum total TG were associated with a decreased AMD risk (OR, 0.84; 95% CI, 0.74-0.95; P = 0.005), whereas, in individuals with 2 risk alleles, higher levels of these particles were associated with an increased risk of AMD (OR, 2.3, 95% CI, 0.99-5.39, P = 0.054).
UNASSIGNED: 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.
摘要：
未经证实：脂质失调和补体系统（CS）激活是年龄相关性黄斑变性（AMD）的2个重要病理生理学途径。我们假设脂质和AMD之间的关系也可能根据CS基因型谱而不同。因此，目的是根据CS基因型研究脂质相关代谢物与AMD之间的关系。
未经评估：基于人群的横断面研究。
UNASSIGNED：共有6947名来自新加坡眼病流行病学研究的参与者获得了完整的相关数据。
UNASSIGNED：我们从核磁共振代谢组学数据中研究了32种与血脂相关的代谢物，包括脂蛋白及其亚类。胆固醇，甘油酯，和磷脂，以及4种CS单核苷酸多态性（SNP）：rs10922109（补体因子H），rs10033900（补体因子I），rs116503776(C2-CFB-SKIV2L),和RS2230199（C3）。我们首先使用多变量逻辑回归模型研究了AMD与32种脂质相关代谢物之间的关联。然后，为了研究脂质相关代谢物对AMD的影响是否根据CSSNP而有所不同，我们测试了CSSNP与脂质相关代谢物之间可能的相互作用.
UNASSIGNED：使用威斯康星分级系统定义年龄相关性黄斑变性。
未经评估：在6947名参与者中，AMD的患病率为6.1%,平均年龄为58.3岁。首先,高密度脂蛋白(HDL)和中、大高密度脂蛋白颗粒中胆固醇水平升高与AMD风险增加相关,较高水平的血清总甘油三酯(TG)和几种极低密度脂蛋白亚类颗粒与AMD风险降低相关.第二,这些脂质与2个CSSNPrs2230199和rs116503776(经多重测试校正后)对AMD有显著的交互作用.对于rs2230199，在没有风险等位基因的个体中，HDL2中较高的总胆固醇与AMD风险增加相关(比值比[OR]/标准差增加,1.20；95%置信区间(CI)，1.06-1.37；P=0.005），然而,在具有至少1个风险等位基因的个体中，这些颗粒的高水平与AMD风险降低相关(OR，0.69；95%CI，0.45-1.05；P=0.079）。相反，对于rs116503776，在没有风险等位基因的个体中，较高的血清总TG与AMD风险降低相关(OR，0.84；95%CI，0.74-0.95；P=0.005），然而,在具有2个风险等位基因的个体中，这些颗粒的高水平与AMD的风险增加相关(OR，2.3，95%CI，0.99-5.39，P=0.054）。
UNASSIGNED：根据CS基因型，脂质相关代谢物对AMD的作用方向相反。这表明脂质代谢和CS在AMD发病机制中可能具有协同相互作用。
未经评估：基于人群的横断面研究。
UNASSIGNED：共有6947名来自新加坡眼病流行病学研究的参与者获得了完整的相关数据。
UNASSIGNED：我们从核磁共振代谢组学数据中研究了32种与血脂相关的代谢物，包括脂蛋白及其亚类。胆固醇，甘油酯，和磷脂，以及4种CS单核苷酸多态性（SNP）：rs10922109（补体因子H），rs10033900（补体因子I），rs116503776(C2-CFB-SKIV2L),和RS2230199（C3）。我们首先使用多变量逻辑回归模型研究了AMD与32种脂质相关代谢物之间的关联。然后，为了研究脂质相关代谢物对AMD的影响是否根据CSSNP而有所不同，我们测试了CSSNP与脂质相关代谢物之间可能的相互作用.
UNASSIGNED：使用威斯康星分级系统定义年龄相关性黄斑变性。
未经评估：在6947名参与者中，AMD的患病率为6.1%,平均年龄为58.3岁。首先,高密度脂蛋白(HDL)和中、大高密度脂蛋白颗粒中胆固醇水平升高与AMD风险增加相关,较高水平的血清总甘油三酯(TG)和几种极低密度脂蛋白亚类颗粒与AMD风险降低相关.第二,这些脂质与2个CSSNPrs2230199和rs116503776(经多重测试校正后)对AMD有显著的交互作用.对于rs2230199，在没有风险等位基因的个体中，HDL2中较高的总胆固醇与AMD风险增加相关(比值比[OR]/标准差增加,1.20；95%置信区间(CI)，1.06-1.37；P=0.005），然而,在具有至少1个风险等位基因的个体中，这些颗粒的高水平与AMD风险降低相关(OR，0.69；95%CI，0.45-1.05；P=0.079）。相反，对于rs116503776，在没有风险等位基因的个体中，较高的血清总TG与AMD风险降低相关(OR，0.84；95%CI，0.74-0.95；P=0.005），然而,在具有2个风险等位基因的个体中，这些颗粒的高水平与AMD的风险增加相关(OR，2.3，95%CI，0.99-5.39，P=0.054）。
UNASSIGNED：根据CS基因型，脂质相关代谢物对AMD的作用方向相反。这表明脂质代谢和CS在AMD发病机制中可能具有协同相互作用。
