评估妇女健康倡议视野检查（WHI-SE）研究中与年龄相关的新的和已建立的黄斑变性易感性基因。
Evaluation of new and established age-related macular degeneration susceptibility genes in the Women's Health Initiative Sight Exam (WHI-SE) Study.
机构信息
Department of Genetics & Genomic Sciences, Mount Sinai School of Medicine, New York, New York, USA.
出版信息
Am J Ophthalmol. 2011 Dec;152(6):1005-1013.e1. doi: 10.1016/j.ajo.2011.05.016. Epub 2011 Sep 9.
PURPOSE
To assess whether established and newly reported genetic variants, independent of known lifestyle factors, are associated with the risk of age-related macular degeneration (AMD) among women participating in the Women's Health Initiative Sight Exam (WHI-SE) Genetic Ancillary Study.
DESIGN
Multicenter case-control study.
METHODS
One hundred and forty-six women with intermediate and late stages of AMD and 1269 subjects without AMD underwent ocular examinations and fundus photography to determine stage of AMD. Fourteen polymorphisms at or near 11 genes, including previously confirmed genes CFH, ARMS2/HTRA1, C2, C3, and CFI; recently reported AMD genes in the high-density lipoprotein cholesterol (HDL) pathway LIPC, ABCA1, CETP, and LPL; TIMP3/SYN3, a known ocular gene recently linked with AMD; and APOE, were assessed using logistic regression analysis.
RESULTS
After adjustment for demographic, behavioral, and other genetic factors, a protective effect was detected among TT carriers compared with non-carriers for the HDL pathway gene, LIPC rs493258, for intermediate and late AMD (OR [95% confidence interval]: 0.3 [0.2-0.7], P = .003). Variants in CFH rs1410996, ARMS2/HTRA1 A69S, and C3 R102G were significantly associated with an increased risk of AMD. Individuals with the homozygous CFI rs10033900 TT genotype had a 2.9 [1.2-7.2]-fold increased risk, and those with the CFH Y402H GG genotype had a 2.2 [1.0-4.8]-fold higher risk of developing AMD compared with non-carriers. APOE4 carriers may have a reduced risk of intermediate/late AMD (OR = 0.5 [0.3-0.9], P = .015. Suggestive associations were seen between AMD and the HDL pathway genes CETP and LPL.
CONCLUSION
In this unique national cohort of women, we found associations with established AMD-related genetic factors and the recently reported LIPC gene in the HDL pathway. These findings may help develop novel therapeutic targets to treat or delay the onset of the disease.
目的
评估已确定的和新报告的遗传变异是否与参加妇女健康倡议视力检查（WHI-SE）遗传辅助研究的女性的年龄相关性黄斑变性（AMD）风险相关，这些遗传变异与已知的生活方式因素无关。
设计
多中心病例对照研究。
方法
146 名患有中晚期 AMD 的女性和 1269 名无 AMD 的受试者接受了眼部检查和眼底照相，以确定 AMD 的阶段。在 11 个基因中的 14 个基因或附近的 14 个多态性，包括先前证实的 CFH、ARMS2/HTRA1、C2、C3 和 CFI 基因；高密度脂蛋白胆固醇（HDL）途径中的最近报道的 AMD 基因 LIPC、ABCA1、CETP 和 LPL；最近与 AMD 相关的已知眼部基因 TIMP3/SYN3；以及 APOE，使用逻辑回归分析进行评估。
结果
在调整人口统计学、行为和其他遗传因素后，与非携带者相比，HDL 途径基因 LIPC rs493258 的 TT 携带者在中间和晚期 AMD 中检测到保护作用（OR [95%置信区间]：0.3 [0.2-0.7]，P =.003）。CFH rs1410996、ARMS2/HTRA1 A69S 和 C3 R102G 的变体与 AMD 风险增加显著相关。携带纯合 CFI rs10033900 TT 基因型的个体患 AMD 的风险增加了 2.9 [1.2-7.2]倍，携带 CFH Y402H GG 基因型的个体患 AMD 的风险增加了 2.2 [1.0-4.8]倍与非携带者相比。APOE4 携带者可能患有中间/晚期 AMD 的风险降低（OR = 0.5 [0.3-0.9]，P =.015）。在 HDL 途径基因 CETP 和 LPL 中观察到与 AMD 之间的提示性关联。
结论
在这个独特的全国女性队列中，我们发现与已确定的 AMD 相关遗传因素和最近报道的 HDL 途径中的 LIPC 基因存在关联。这些发现可能有助于开发治疗或延迟疾病发作的新治疗靶点。
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