吸烟、体重指数、膳食叶黄素以及LIPC基因变异rs10468017与晚期年龄相关性黄斑变性的关联。
Associations of smoking, body mass index, dietary lutein, and the LIPC gene variant rs10468017 with advanced age-related macular degeneration.
作者信息
Seddon Johanna M, Reynolds Robyn, Rosner Bernard
机构信息
Ophthalmic Epidemiology and Genetics Service, Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, and Channing Laboratory, Brigham and Women's Hospital, Boston, MA 02111, USA.
出版信息
Mol Vis. 2010 Nov 17;16:2412-24.
OBJECTIVE
A novel locus in the hepatic lipase (LIPC) gene was found to be significantly related to advanced age-related macular degeneration (AMD) in our genome-wide association study. We evaluated its association and interaction with previously identified genetic variants and modifiable factors.
METHODS
Participants in the Age-Related Eye Disease Study with advanced AMD (n=545 cases) or no AMD (n=275 controls) were evaluated. AMD status was determined using fundus photography. Covariates included cigarette smoking, body mass index (BMI), and dietary lutein. Individuals were genotyped for the rs10468017 polymorphism in LIPC as well as seven previously identified AMD genetic loci. Unconditional logistic regression analyses were then performed.
RESULTS
The TT genotype of the LIPC variant was associated with a reduced risk of AMD, with odds ratios (OR) of 0.50 (95% confidence interval (CI) 0.20-0.90) and p=0.014 for the TT genotype versus the CC genotype, controlling for age, gender, smoking, body mass index (BMI), and nutritional factors. Controlling for seven other AMD genetic variants, the OR was 0.50, 95% (CI 0.20-1.1, p=0.077). The magnitude of the effect was similar for both atrophic and neovascular forms of AMD. Cigarette smoking and higher BMI increased the risk, while higher dietary lutein reduced the risk of advanced AMD, adjusting for genetic variants. There were no significant interactions between LIPC and smoking, BMI, or lutein. There was a possible association between LIPC and complement factor H (CFH) rs1410996, and a possible interaction effect between LIPC and both CFH rs10033900 and the complement factor I (CFI) variants in terms of risk of AMD.
CONCLUSIONS
LIPC is associated with reduced risk of advanced AMD, independent of demographic and environmental variables. Both genetic susceptibility and behavioral and lifestyle factors modify the risk of developing AMD.
目的
在我们的全基因组关联研究中，发现肝脂酶（LIPC）基因中的一个新位点与晚期年龄相关性黄斑变性（AMD）显著相关。我们评估了它与先前确定的基因变异和可改变因素之间的关联及相互作用。
方法
对年龄相关性眼病研究中患有晚期AMD（n = 545例）或无AMD（n = 275例对照）的参与者进行评估。使用眼底摄影确定AMD状态。协变量包括吸烟、体重指数（BMI）和膳食叶黄素。对个体进行LIPC中rs10468017多态性以及七个先前确定的AMD基因位点的基因分型。然后进行无条件逻辑回归分析。
结果
LIPC变异的TT基因型与AMD风险降低相关，TT基因型与CC基因型相比，调整年龄、性别、吸烟、体重指数（BMI）和营养因素后，比值比（OR）为0.50（95%置信区间（CI）0.20 - 0.90），p = 0.014。控制其他七个AMD基因变异后，OR为0.50，95%（CI 0.20 - 1.1，p = 0.077）。萎缩性和新生血管性AMD的效应大小相似。调整基因变异后，吸烟和较高的BMI增加风险，而较高的膳食叶黄素降低晚期AMD风险。LIPC与吸烟、BMI或叶黄素之间无显著相互作用。LIPC与补体因子H（CFH）rs1410996之间可能存在关联，LIPC与CFH rs10033900和补体因子I（CFI）变异在AMD风险方面可能存在相互作用效应。
结论
LIPC与晚期AMD风险降低相关，独立于人口统计学和环境变量。遗传易感性以及行为和生活方式因素均会改变发生AMD的风险。
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