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.
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。