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JAMA Ophthalmology

Cipriani, V., Hogg, R.E., Sofat, R., et al.

期刊名称:JAMA Ophthalmology


JAMA Ophthalmology


摘要:重要性:C-反应蛋白(CRP)是一种与晚期老年性黄斑变性(AMD)相关的循环炎症标志物。CRP浓度与AMD之间的关联是否存在因果关系仍然不确定。目的:旨在评估影响循环CRP浓度的CRPOMIM 123260)单核苷酸多态性是否与晚期AMD相关。设计,设置和研究对象:2000116日至2007430日间,招募了2项英国,基于医院的病例对照研究(剑桥AMD研究和Moorfields眼科医院AMD研究)和1项泛欧,横断面的基于人群的研究(欧洲眼[EUREYE]研究))。根据国际年龄相关性黄斑变性和黄斑变性分类,参加者进行了扩张立体数字眼底摄影。共有1727例晚期AMD1151例新生血管性,384例地中海萎缩,192例混合性新生血管性AMD和地理性萎缩症)和1153例对照。早期AMD病例(n = 574)仅包括在EUREYE研究中。于201681日至1130日进行数据分析。根据文献中显示的循环CRP浓度的影响,选择了四种常见的单核苷酸多态性(rs1205rs1130864rs1800947rs3093077)。在一项研究中,rs3093077基因分型失败,rs1800947仅在1项研究中进行。主要预后指标:使用一种遗传多样性模型分析单核苷酸多态性与进行年龄和性别调整的晚期AMD的关联。结果: 1727名晚期AMD患者的平均(SD)年龄为78.77.4)岁,男性668例(38.7%)。对照组平均(SD)年龄为74.97.0)岁,男性510例(44.2%)。在所有3项研究的综合结果中,rs1205OR0.99; 95CI0.86-1.14)和rs1130864OR0.96; 95CI0.83-1.11)均与晚期AMD无关。对于地理性萎缩,rs1205OR0.9195CI0.74-1.13),rs1130864OR0.9495CI0.76-1.16)。对于新生血管性AMDrs1205OR1.0195CI0.87-1.19),rs1130864OR0.9995CI0.84-1.16)。rs3093077rs1800947与晚期AMD或任何晚期AMD表型无关联。结论与意义:我们的研究结果不支持CRP浓度与AMD之间存在因果关系。

Importance:C-reactive protein (CRP) is a circulating inflammatory marker associated with late age-related macular degeneration (AMD). It remains uncertain whether the association between CRP concentrations and AMD is causal.Objective:To assess whether CRP (OMIM 123260) single-nucleotide polymorphisms that influence circulating CRP concentrations are associated with late AMD.Design, Setting, and Participants:Participants in 2 UK, hospital-based, case-control studies (Cambridge AMD study and Moorfields Eye Hospital AMD study) and 1 pan-European, cross-sectional, population-based study (the European Eye [EUREYE] Study) were recruited between November 6, 2000, and April 30, 2007. Participants underwent dilated stereo-digital fundus photography graded according to the International Classification of Age-related Maculopathy and Macular Degeneration. There were 1727 cases of late AMD (1151 neovascular, 384 geographic atrophy, and 192 mixed [neovascular AMD and geographic atrophy]) and 1153 controls. Early AMD cases (n = 574) were included only from the EUREYE Study. Data analysis was performed from August 1 to November 30, 2016. Four common single-nucleotide polymorphisms (rs1205, rs1130864, rs1800947, and rs3093077) were selected based on demonstrated influence on circulating CRP concentrations in the literature. In one study, genotyping of rs3093077 failed, and rs1800947 was typed in only 1 study.Main Outcomes and Measures:A genetic multiplicative model was used for the association of single-nucleotide polymorphisms with late AMD adjusted for age and sex.Results:Among the 1727 patients with late AMD, the mean (SD) age was 78.7 (7.4) years, and 668 (38.7%) were men. The mean (SD) age of the controls was 74.9 (7.0) years, and 510 (44.2%) were men. In the pooled results of all 3 studies, neither rs1205 (odds ratio [OR], 0.99; 95% CI, 0.86-1.14) nor rs1130864 (OR, 0.96; 95% CI, 0.83-1.11) was associated with late AMD. For geographic atrophy, rs1205 had an OR of 0.91 (95% CI, 0.74-1.13) and rs1130864 had an OR of 0.94 (95% CI, 0.76-1.16). For neovascular AMD, rs1205 had an OR of 1.01 (95% CI, 0.87-1.19) and rs1130864 had an OR of 0.99 (95% CI, 0.84-1.16). There was no association of rs3093077 and rs1800947 with late AMD or any late AMD phenotype. There were no significant findings for early AMD.Conclusions and Relevance:Our results do not support a causal association between CRP concentrations and AMD.


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