PURPOSE Genetic and epidemiologic studies have shown that lipid genes and high-density lipoproteins (HDLs) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relationship to AMD in a large European dataset. DESIGN Pooled analysis of cross-sectional data. PARTICIPANTS Individuals (N = 30 953) aged 50 years or older participating in the European Eye Epidemiology (E3) consortium and 1530 individuals from the Rotterdam Study with lipid subfraction data. METHODS AMD features were graded on fundus photographs using the Rotterdam classification. Routine blood lipid measurements, genetics, medication, and potential confounders were extracted from the E3 database. In a subgroup of the Rotterdam Study, lipid subfractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random effect were used to estimate associations. MAIN OUTCOME MEASURES AMD features and stage; lipid measurements. RESULTS HDL was associated with an increased risk of AMD (odds ratio [OR], 1.21 per 1-mmol/l increase; 95% confidence interval [CI], 1.14-1.29), whereas triglycerides were associated with a decreased risk (OR, 0.94 per 1-mmol/l increase; 95% CI, 0.91-0.97). Both were associated with drusen size. Higher HDL raised the odds of larger drusen, whereas higher triglycerides decreases the odds. LDL cholesterol reached statistical significance only in the association with early AMD (P = 0.045). Regarding lipid subfractions, the concentration of extra-large HDL particles showed the most prominent association with AMD (OR, 1.24; 95% CI, 1.10-1.40). The cholesteryl ester transfer protein risk variant (rs17231506) for AMD was in line with increased HDL levels (P = 7.7 × 10-7), but lipase C risk variants (rs2043085, rs2070895) were associated in an opposite way (P = 1.0 × 10-6 and P = 1.6 × 10-4). CONCLUSIONS Our study suggested that HDL cholesterol is associated with increased risk of AMD and that triglycerides are negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL subfractions seem to be drivers in the relationship with AMD, and variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains to be answered.

中文翻译：

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与年龄相关的黄斑变性相关的高密度脂蛋白水平升高：来自眼风险和欧洲眼流行病学联盟的证据。

目的遗传和流行病学研究表明，脂质基因和高密度脂蛋白（HDL）与年龄相关性黄斑变性（AMD）有关。我们在一个大型的欧洲数据集中研究了与AMD相关的循环脂质水平。设计截面数据的汇总分析。参与者参加欧洲眼流行病学（E3）协会的50岁或50岁以上的个体（N = 30953）和来自鹿特丹研究的1530个人（含脂质亚组分数据）。方法使用鹿特丹分类法在眼底照片上对AMD特征进行分级。常规血脂测量，遗传学，药物治疗和潜在的混杂因素均从E3数据库中提取。在鹿特丹研究的一个亚组中，通过Nightingale生物标志物平台鉴定了脂质亚组分。结合混杂因素和研究地点作为随机效应的随机拦截混合效应模型用于估计关联。主要观察指标AMD的功能和阶段；脂质测量。结果HDL与AMD风险增加相关（比值比[OR]，每1 mmol / l增加1.21； 95％置信区间[CI]，1.14-1.29），而甘油三酸酯与风险降低相关（OR，每1 mmol / l增加0.94; 95％CI，0.91-0.97）。两者均与玻璃膜疣的大小有关。较高的HDL会增加玻璃疣的几率，而较高的甘油三酸酯则降低该几率。LDL胆固醇仅在早期AMD中才具有统计学意义（P = 0.045）。关于脂质亚组分，超大型HDL颗粒的浓度与AMD的关系最为明显（OR为1.24； 95％CI为1.10-1.40）。AMD的胆固醇酯转移蛋白风险变量（rs17231506）与HDL水平升高（P = 7.7×10-7）一致，但是脂肪酶C风险变量（rs2043085，rs2070895）却以相反的方式关联（P = 1.0× 10-6，P = 1.6×10-4）。结论我们的研究表明HDL胆固醇与AMD风险增加有关，而甘油三酸酯则与负相关。两者均显示出与早期AMD和玻璃疣相关性最强。超大型HDL子级似乎是与AMD关系的驱动因素，脂质基因的变异在这种关联中起着更加模糊的作用。全身性脂质是否直接影响AMD还是代表视网膜中的脂质代谢尚待回答。但是脂肪酶C风险变量（rs2043085，rs2070895）却以相反的方式关联（P = 1.0×10-6和P = 1.6×10-4）。结论我们的研究表明HDL胆固醇与AMD风险增加有关，而甘油三酸酯则与负相关。两者均显示出与早期AMD和玻璃疣相关性最强。超大型HDL子级似乎是与AMD关系的驱动因素，脂质基因的变异在这种关联中起着更加模糊的作用。全身性脂质是否直接影响AMD还是代表视网膜中的脂质代谢尚待回答。但是脂肪酶C风险变量（rs2043085，rs2070895）却以相反的方式关联（P = 1.0×10-6和P = 1.6×10-4）。结论我们的研究表明HDL胆固醇与AMD风险增加有关，而甘油三酸酯则与负相关。两者均显示出与早期AMD和玻璃疣相关性最强。超大型HDL子级似乎是与AMD关系的驱动因素，脂质基因的变异在这种关联中起着更加模糊的作用。全身性脂质是否直接影响AMD还是代表视网膜中的脂质代谢尚待回答。两者均显示出与早期AMD和玻璃疣相关性最强。超大型HDL子级似乎是与AMD关系的驱动因素，脂质基因的变异在这种关联中起着更加模糊的作用。全身性脂质是否直接影响AMD还是代表视网膜中的脂质代谢尚待回答。两者均显示出与早期AMD和玻璃疣相关性最强。超大型HDL子级似乎是与AMD关系的驱动因素，脂质基因的变异在这种关联中起着更加模糊的作用。全身性脂质是否直接影响AMD还是代表视网膜中的脂质代谢尚待回答。