DeAngelis Margaret M, Owen Leah A, Morrison Margaux A, Morgan Denise J, Li Mingyao, Shakoor Akbar, Vitale Albert, Iyengar Sudha, Stambolian Dwight, Kim Ivana K, Farrer Lindsay A
Department of Ophthalmology and Visual Sciences, John Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Department of Pharmacotherapy, L.S. Skaggs School of Pharmacy, University of Utah, Salt Lake City, UT 84132, USA.
Hum Mol Genet. 2017 Aug 1;26(R1):R45-R50. doi: 10.1093/hmg/ddx228.
Age-related macular degeneration (AMD) is a progressive blinding disease and represents the leading cause of visual impairment in the aging population. AMD affects central vision which impairs one's ability to drive, read and recognize faces. There is no cure for this disease and current treatment modalities for the exudative form of the disease require repeated intravitreal injections which may be painful, are incompletely efficacious, and represent a significant treatment burden for both the patient and physician. As such, AMD represents a significant and important clinical problem.It is anticipated that in three years' time, 196 million individuals will be affected with AMD. Over 250 billion dollars per year are spent on care for AMD patients in the US. Over half of the heritability is explained by two major loci, thus AMD is considered the most well genetically defined of the complex disorders. A recent GWAS on 43,566 subjects identified novel loci and pathways associated with AMD risk, which has provided an excellent platform for additional functional studies. Genetic variants have been investigated, particularly with respect to anti-VEGF treatment, however to date, no pharmacogenomic associations have been consistently identified across these studies. It may be that if the goal of personalized medicine is to be realized and biomarkers are to have predictive value for determining the magnitude of risk for AMD at the genetic level, one will need to examine the relationships between these pathways across disease state and relative to modifiable risk factors such as hypertension, smoking, body mass index, and hypercholesterolemia. Further studies investigating protective alleles in populations with low AMD prevalence may lead to this goal.
年龄相关性黄斑变性（AMD）是一种进行性致盲疾病，是老年人群视力损害的主要原因。AMD影响中心视力，损害患者的驾驶、阅读和面部识别能力。这种疾病无法治愈，目前针对渗出性AMD的治疗方法需要反复进行玻璃体内注射，这可能会带来疼痛，疗效不完全，且给患者和医生都带来了巨大的治疗负担。因此，AMD是一个重大且重要的临床问题。预计在三年内，将有1.96亿人受到AMD影响。在美国，每年花费超过2500亿美元用于AMD患者的护理。超过一半的遗传度由两个主要基因座解释，因此AMD被认为是复杂疾病中基因定义最明确的疾病。最近一项针对43566名受试者的全基因组关联研究（GWAS）确定了与AMD风险相关的新基因座和途径，为进一步的功能研究提供了一个极好的平台。已经对基因变异进行了研究，特别是关于抗血管内皮生长因子（VEGF）治疗方面，然而迄今为止，在这些研究中尚未一致确定药物基因组学关联。如果要实现个性化医疗的目标，并且生物标志物在基因水平上对确定AMD风险程度具有预测价值，那么可能需要研究这些途径在不同疾病状态之间以及相对于可改变的风险因素（如高血压、吸烟、体重指数和高胆固醇血症）之间的关系。对AMD患病率较低人群中保护性等位基因的进一步研究可能会实现这一目标。
