渗出型老年性黄斑变性患者负荷抗血管内皮生长因子药物治疗反应与单核苷酸多态性的相关性研究  

Association between single nucleotide polymorphism and response to anti vascular endothelial growth factor therapy in patients with wet age-related macular degeneration

作　　者：殷心轩 邢东军 汪婷丽 于荣国 王林妮 胡立影 宫雪 陈璐 李志清 Yin Xinxuan;Xing Dongjun;Wang Tingli;Yu Rongguo;Wang Linni;Hu Liying;Gong Xue;Chen Lu;Li Zhiqing(Tianjin Medical University Eye Hospital,Eye Institute and School of Optometry,Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science,Tianjin 300384,China)

机构地区：[1]天津医科大学眼科医院、眼视光学院、眼科研究所,天津市眼科学与视觉科学国际联合研究中心,300384

出　　处：《中华眼底病杂志》2021年第9期693-701,共9页Chinese Journal of Ocular Fundus Diseases

基　　金：天津市临床重点学科建设项目(TJLCZDXKQ022);天津市教委社会科学重大项目(2018JWZD25);天津市教委科研计划项目(2017KJ216);京津冀基础研究合作专项项目(20JCZXJC00110);滨海新区卫生健康委员会科技项目(重点支持项目)(2019BWKZ006)。

摘　　要：目的观察渗出型老年性黄斑变性(wAMD)患者负荷抗血管内皮生长因子(VEGF)药物治疗反应与单核苷酸多态性(SNP)基因型的关系。方法回顾性临床研究。2019年8月至2020年9月在天津医科大学眼科医院检查确诊的wAMD患者103例103只眼纳入研究。其中,男性59例(57.28%,59/103),女性44例(42.72%,44/103 );平均年龄(68.74±7.74)岁。采用标准对数视力表检测患眼BCVA,统计时换算为最小分辨角对数(logMAR)视力。采用光相干断层扫描(OCT)检测患眼黄斑中心凹视网膜厚度(CRT)。同时检测患者的高密度脂蛋白胆固醇(HDL-C)。所有患眼均行玻璃体腔注射抗VEGF药物治疗,每月1次,连续3个月。初次治疗前,采集患者外周静脉血,质谱法检测白细胞介素-8 (IL-8)、补体C3基因(C3)、补体因子H (CFH)、肝脂肪酶(LIPC)、胆固醇脂蛋白转移酶(CETP)、三磷酸腺苷结合盒亚家族A成员1(ABCA1)、脂蛋白脂肪酶(LPL)、脂肪酸去饱和基因簇(FADS1)的SNP。按照基因频率将基因型分为野生型和突变型。临床表型中各基因型分布的频率差异和基因型分布的Hardy-Weinberg平衡等定性数据比较行χ^(2)检验或Fisher确切检验。结果 IL-8 rs4073突变型(TA+AA)患者中CRT有反应者较野生型(TT)少[比值比(OR)=0.310,95%可信区间(CI)0.106~ 0.910,P<0.05)。其中药物分层检验后,康柏西普治疗组中IL-8 rs4073位点TT基因型患者CRT无反应者占比更少(OR=0.179,95%CI =0.034~ 0.960,P=0.033)。LIPC rs2043085突变型(CT+TT)患者中BCVA提高≥0.2 logMAR单位者较野生型(CC)可能性更高(OR=3.031,95%CI 1.036~ 8.867,P<0.05);HDL-C水平显著低于野生型(CC),差异有统计学意义(t=2.448,P=0.016)。IL-8 rs4073、LIPC rs2043085突变型和野生型患者治疗前logMAR BCVA、CRT比较,差异无统计学意义(IL-8 rs4073:Z=-0.198、-1.651,P=0.843、0.099;LIPC rs2043085 :Z=-0.532、-0.152,P=0.595、0.879)。C3 rs 225066、CFH rs800292、CETP rs708272、ABCA1 rs1883025、FADS1 rs174547、LPL rsObjective To observe the relationship between the response to anti-vascular endothelial growth factor(VEGF)drug treatment and single nucleotide polymorphism(SNP)genotype in patients with wet age-related macular degeneration(wAMD).Methods A retrospective clinical study.From August 2019 to September 2020,103 eyes of 103 wAMD patients diagnosed in Tianjin Medical University Eye Hospital were included in the study.Among them,there were 59 males(57.28%,59/103)and 44 females(42.72%,44/103);the average age was 68.74±7.74 years.The standard logarithmic visual acuity chart was used to detect the Best Corrected Visual Acuity of the affected eye and converted to the logarithmic minimum angle of resolution(logMAR)visual acuity during statistics.Optical coherence tomography was used to detect the central retinal thickness(CRT)of the affected eye.At the same time,the patient's high-density lipoprotein cholesterol(HDL-C)was tested.All eyes were treated with intravitreal injection of anti-VEGF drugs once a month for 3 months.Before the initial treatment,peripheral venous blood from the patient were collected.Interleukin-8(IL-8),complement C3 gene(C3),complement factor H(CFH),liver lipase(LIPC),cholesterol ester transfer protein(C£TP),ATP binding cassette subfamily a member 1(ABCA1),lipoprotein lipase(LPL),fatty acid desaturation gene cluster(FADS1)SNP.According to gene frequency,genotypes are divided into wild type and mutant type were detected.Qualitative data such as the frequency difference of the genotype distribution in the clinical phenotype and the Hardy-Weinberg equilibrium of the genotype distribution were compared with the Chi-square test or Fisher's exact test.Results There were fewer CRT responders in IL-8 rs4073 mutant(TA+AA)patients than wild-type(TT)[odds ratio(OR)=0.310,95%confidence interval(CI)0.106-0.910,P<0.05).Among them,after the drug stratification test,the proportion of patients with IL-8 rs4073 locus TT genotype in the conbercept treatment group was less CRT non-responders(OR=OA19,95%CI=0.034-0.960,P=0

关 键 词：湿性黄斑变性 血管生成抑制剂 重组融合蛋白质类 多态性 单核苷酸 

分 类 号：R774.5[医药卫生—眼科]