血清脂质生物标志物与肝脂酶基因与年龄相关性黄斑变性的关系。
Serum lipid biomarkers and hepatic lipase gene associations with age-related macular degeneration.
机构信息
Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Department of Ophthalmology, Tufts Medical Center, Boston, Massachusetts 02111, USA.
出版信息
Ophthalmology. 2010 Oct;117(10):1989-95. doi: 10.1016/j.ophtha.2010.07.009.
OBJECTIVE
A genetic variant in the high-density lipoprotein (HDL) cholesterol pathway, hepatic lipase (LIPC), was discovered to be associated with advanced age-related macular degeneration (AMD) in a genome-wide association study. In this study, we evaluated whether LIPC is associated with serum lipids, and whether this gene and serum lipids are independently associated with AMD.
DESIGN
Case-control study.
PARTICIPANTS
A total of 458 participants from the Progression Study of Macular Degeneration and the Age-Related Eye Disease Ancillary Biomarker Study, including 318 advanced AMD cases with either geographic atrophy (n = 123) or neovascular disease (n = 195) and 140 controls.
METHODS
Participants were genotyped for 8 variants associated with AMD: 2 CFH variants, C2, CFB, C3, CFI, the ARMS2/HTRA1 gene region, and LIPC. Fasting blood specimens were obtained at study onset, and serum levels of total cholesterol, low-density lipoprotein (LDL), HDL, and triglycerides were determined. Logistic and linear regression were used to evaluate associations between serum lipids, LIPC genotype, and AMD.
MAIN OUTCOME MEASURES
LIPC and serum lipid associations with AMD.
RESULTS
The minor T allele of the LIPC gene was associated with a reduced risk of AMD (odds ratio, 0.4; 95% confidence interval, 0.2-0.9; P = 0.01, trend for number of T alleles, controlling for age and gender). Mean level of HDL was lower (P = 0.05) and mean level of LDL (P = 0.03) was higher in cases of advanced AMD compared with controls. Higher total cholesterol and LDL levels were associated with increased risk of AMD, with P for trend = 0.01 for both, in models controlling for environmental and genetic covariates. The T allele of LIPC was associated with higher levels of HDL, although LIPC was associated with advanced AMD independent of HDL level.
CONCLUSIONS
The HDL-raising allele of the LIPC gene (T) was associated with a reduced risk of AMD. Higher total cholesterol and LDL levels were associated with increased risk, whereas higher HDL levels tended to reduce the risk of AMD. The specific mechanisms underlying the association between AMD and LIPC require further investigation.
目的
一项全基因组关联研究发现，高密度脂蛋白（HDL）胆固醇途径中的遗传变异——肝脂肪酶（LIPC）与年龄相关性黄斑变性（AMD）的发生密切相关。本研究旨在评估 LIPC 是否与血清脂质相关，以及该基因与血清脂质是否与 AMD 独立相关。
设计
病例对照研究。
参与者
共纳入来自年龄相关性眼病研究的进展研究和辅助生物标志物研究的 458 名参与者，包括 318 名 AMD 晚期患者（其中 123 名患有地图状萎缩，195 名患有新生血管性疾病）和 140 名对照者。
方法
参与者接受了与 AMD 相关的 8 种变体的基因分型：2 种 CFH 变体、C2、CFB、C3、CFI、ARMS2/HTRA1 基因区域和 LIPC。在研究开始时采集空腹血样，测定总胆固醇、低密度脂蛋白（LDL）、HDL 和甘油三酯的血清水平。采用 logistic 和线性回归分析评估血清脂质、LIPC 基因型与 AMD 之间的关系。
主要观察指标
LIPC 与血清脂质与 AMD 的相关性。
结果
LIPC 基因的 T 等位基因较少与 AMD 风险降低相关（比值比，0.4；95%置信区间，0.2-0.9；P = 0.01，趋势检验 T 等位基因数量，控制年龄和性别）。与对照组相比，晚期 AMD 患者的 HDL 水平较低（P = 0.05），LDL 水平较高（P = 0.03）。总胆固醇和 LDL 水平较高与 AMD 风险增加相关，在控制环境和遗传协变量的模型中，P 值均为 0.01。LIPC 基因的 T 等位基因与 HDL 水平升高相关，但 LIPC 与 AMD 相关独立于 HDL 水平。
结论
LIPC 基因的 HDL 升高等位基因（T）与 AMD 风险降低相关。总胆固醇和 LDL 水平升高与风险增加相关，而 HDL 水平升高则降低 AMD 的风险。AMD 与 LIPC 之间的关联的具体机制需要进一步研究。
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