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CFH基因多态性与玻璃体液VEGF对年龄相关性黄斑变性患者抗VEGF疗效影响的交互作用

Interaction between complement factor H gene polymorphism and vascular endothelial growth factor in vitreous humor on anti-vascular endothelial growth factor efficacy in patients with age-related macular degeneration
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摘要 目的探讨补体因子H(CFH)基因多态性与玻璃体液血管内皮生长因子(VEGF)对年龄相关性黄斑变性(AMD)患者抗VEGF疗效影响的交互作用。方法选取2020年5月~2022年1月广州医科大学附属第三医院眼科149例(149眼)AMD患者为研究对象,根据抗VEGF治疗是否有应答,分为应答组(111例)、无应答组(38例)。比较两组患者CFH基因多态性、玻璃体液VEGF表达水平,比较CFH位点rs1061170不同基因型患者玻璃体液VEGF表达水平,采用Logistic分析抗VEGF疗效的相关影响因素,采用交互作用系数γ分析CFH基因多态性、玻璃体液VEGF的交互作用是否存在及其作用类型。结果无应答组患者CFH位点rs1061170基因型分布与应答组比较,差异有统计学意义(P<0.05)。无应答组患者玻璃体液VEGF高于应答组(P<0.05)。在全部AMD患者中,玻璃体液VEGF高水平患者CFH位点rs1061170基因型分布与低水平患者比较,差异有统计学意义(P<0.05)。在全部AMD患者中,玻璃体液VEGF、CFH位点rs1061170 CC基因型均是抗VEGF疗效的独立相关影响因素(均为P<0.05)。在全部AMD患者中,单独玻璃体液VEGF的OR值为41.250,单独rs1061170基因型CC的OR值为22.000,两者共存时的OR值为759.000,且γ为1.068,提示患者玻璃体液VEGF升高与CFH位点rs1061170 CC基因型在抗VEGF疗效中呈正向交互作用;同时交互作用<两单独因素OR值的乘积,则患者玻璃体液VEGF升高与CFH位点rs1061170 CC基因型交互作用符合次相乘模型。结论玻璃体液VEGF升高与CFH位点rs1061170 CC基因型在AMD抗VEGF疗效中呈正向交互作用,且交互作用符合次相乘模型,为临床抗VEGF药物精准使用提供参考。 Objective To investigate the interaction of complement factor H(CFH)gene polymorphism and vascular endothelial growth factor(VEGF)in vitreous humor on anti-VEGF efficacy in age-related macular degeneration(AMD).Methods A total of 149 AMD patients(149 eyes)admitted to the Ophthalmology Department of the Third Affiliated Hospital of Guangzhou Medical University from May 2020 to January 2022 were selected and divided into the response group(111 patients)and non-response group(38 patients)according to the anti-VEGF therapeutic effect.The CFH gene polymorphism,VEGF levels in vitreous humor,and VEGF levels in vitreous humor of patients with different genotypes at CFH rs1061170 were compared.Logistic analysis was conducted to identify the influencing factors of anti-VEGF efficacy,and the interaction coefficientγwas used to explore if there was an interaction between CFH gene polymorphism and VEGF in vitreous humor and their action type.Results The difference in the distribution of CFH rs1061170 genotypes was statistically significant in the non-response group and the response group(P<0.05).The VEGF level in vitreous humor of patients in the non-response group was higher than that in the response group(P<0.05).Among all AMD patients,the distribution of CFH rs1061170 genotypes in patients with high VEGF levels in vitreous humor was significantly different from those with low levels(P<0.05).The VEGF level in vitreous humor and CFH rs1061170 genotype CC were both independent influencing factors on anti-VEGF efficacy(both P<0.05).The odds ratio(OR)was 41.250 for VEGF in vitreous humor alone and 22.000 for rs1061170 genotype CC alone,and 759.000 when they coexist.Theγwas 1.068,suggesting a positive interaction of elevated VEGF level in vitreous humor and CFH rs1061170 genotype CC in the anti-VEGF efficacy.The simultaneous interaction was less than the product of OR of the two individual factors,and the interaction of increased VEGF level in vitreous humor and CFH rs1061170 genotype CC on the anti-VEGF efficacy was consistent with the submultiplicative model.Conclusion The increase of VEGF level in vitreous humor and the CFH rs1061170 genotype CC have a positive interaction in the anti-VEGF efficacy of AMD,and the interaction conforms to the submultiplicative model,supporting the precise use of clinical anti-VEGF drugs.
作者 赵文 赵斐 李敏 叶慧芳 ZHAO Wen;ZHAO Fei;LI Min;YE Huifang(Department of Ophthalmology,the Third Affiliated Hospital of Guangzhou Medical University,Guangzhou 510000,Guangdong Province,China;Danjiangkou First Hospital,Shiyan 442703,Hubei Province,China;Chongqing Emergency Medical Center,Chongqing 400000,China;Zhumadian Center Hospital,Zhumadian 463000,Henan Province,China)
出处 《眼科新进展》 CAS 北大核心 2022年第12期962-966,共5页 Recent Advances in Ophthalmology
基金 河南省医学科技攻关项目(编号:2018020445)。
关键词 CFH基因多态性 血管内皮生长因子 年龄相关性黄斑变性 雷珠单抗 疗效 交互作用 complement factor H gene polymorphism vascular endothelial growth factor age-related macular degeneration ranibizumab efficacy interaction
作者简介 赵文(ORCID:0000-0003-4240-1331),女,1979年10月出生,山东人,主治医师。研究方向:眼科。E-mail:2911298806@qq.com;通信作者:赵斐(ORCID:0000-0002-8978-8862),男,1974年9月出生,山东人,副主任医师。研究方向:眼科临床工作。E-mail:2713369252@qq.com。
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