湿性年龄相关性黄斑变性抗新生血管治疗无应答遗传因素研究

发布时间：2018-11-16 15:13

【摘要】：目的:用Meta分析法对HTRA1基因rs11200638位点多态性(SNP)与湿性年龄相关性黄斑变性(AMD)抗新生血管治疗无应答的相关性进行系统评价。方法:计算机检索Pubmed、Embase及Cochrane图书馆等电子数据库,纳入治疗新生血管性AMD及PCV的队列研究。治疗方式包括抗新生血管药物治疗(雷珠单抗/贝伐单抗)或/和光动力治疗。以治疗应答人数与无应答人数的比值比(OR)和95%置信区间(CI)作为效应指标,采用Rev Man 5.3版软件进行Meta分析,利用固定效应模型或随机效应模型进行评估,运用Q检验评估研究异质性,采用NOS量表对文献质量进行评价。结果:最终纳入9篇病例对照研究,共2096例病例,整体人群Meta分析结果显示:SNP rs11200638基因多态性与湿性AMD抗新生血管治疗应答有相关性,携带基因型GG或GA的治疗应答率是基因型AA的1.56倍(GG+GA versus AA:OR 1.56,95%CI:1.10-2.20,random model)。针对不同人群进行亚组分析显示:东亚人群中,携带野生型等位基因G应答率高于突变型等位基因A,野生纯合基因型GG和野生杂合基因型GA应答率高于突变纯合基因型AA,(GG vs.AA:OR 1.94,95%CI:1.19-3.16,fix model;GA vs.AA:OR1.47,95%CI:1.04-2.09,fix model;GG+GA vs.AA:OR 1.57,95%CI:1.13-2.17,fix model;G vs.A:OR 1.47,95%CI:1.15-1.86,fix model.);在高加索人群中,等位基因之间及各基因型之间治疗应答率无统计学差异。以临床类型不同进行亚组分析显示:在东亚人群含PCV患者组中,各基因对比组效应值OR均大于不含PCV组。含PCV组结果:GG vs.AA:OR 3.58,95%CI 1.31-9.83,fix model;GA vs.AA:OR 1.80,95%CI:0.86-3.75,fix model;GG+GA vs.AA:OR 2.14 95%CI:1.07-4.27,fix model;G vs.A:OR 1.86,95%CI:1.16-2.98,fix model;不含PCV组结果:GG vs.AA:OR 1.55,95%CI 0.87-2.74,fix model;GA vs.AA:OR 1.65,95%CI:0.64-4.25,random model;GG+GA vs.AA:OR 1.63 95%CI:0.75-3.53,random model;G vs.A:OR 1.34,95%CI:1.01-1.78,fix model;高加索人群无统计学差异。结论:HTRA1基因rs11200638位点多态性与东亚人群湿性AMD的治疗应答具有相关性,患者携带野生型等位基因G预示治疗应答率高,携带突变型等位基因A应答率低,尤其对于PCV亚型,此现象更明显。在高加索人群未发现统计学意义。因此,HTRA1基因有可能成为湿性AMD实现个体化治疗并获取最佳视力效果的基因标记物,但仍需更多的高质量大样本研究进一步验证。
[Abstract]:Objective: to evaluate the relationship between HTRA1 rs11200638 locus polymorphism (SNP) and anti-neovascularization response of (AMD) with wet age related macular degeneration by Meta analysis. Methods: electronic databases such as Pubmed,Embase and Cochrane library were searched and included in the cohort study of neovascular AMD and PCV. Treatments include anti-neovascularization drug therapy (Terezumab / bevacizumab) or / and photodynamic therapy. (OR) and 95% confidence interval (CI) were used as effect indexes. Meta was analyzed by Rev Man 5.3 software and evaluated by fixed effect model or random effect model. Q test was used to evaluate heterogeneity and NOS scale was used to evaluate the quality of literature. Results: a total of 2096 cases were included in 9 case-control studies. The results of Meta analysis showed that the polymorphism of SNP rs11200638 gene was associated with the anti-angiogenic response of wet AMD. The therapeutic response rate of carrying genotype GG or GA was 1.56 times that of genotype AA, (GG GA versus AA:OR 1.566 / 95 CI: 1.10-2.20% random model). Subgroup analysis of different populations showed that in East Asian population, the G response rate of wild allele was higher than that of mutant allele A, and the response rate of wild homozygous genotype GG and wild heterozygous genotype GA was higher than that of mutant homozygous genotype AA,. (GG vs.AA:OR 1.94 / 95 CI: 1.19-3.16) fix model; GA vs.AA:OR1.47,95%CI:1.04-2.09,fix model;GG GA vs.AA:OR 1.57 / 95 CIW 1.13-2.17 fix model;G vs.A:OR 1.4795 I will fix model.); 1.15-1.86 There was no significant difference in therapeutic response rates between alleles and genotypes in Caucasian populations. Subgroup analysis with different clinical types showed that the effect value of OR in each gene control group was higher than that without PCV in East Asian population with PCV. Results of GG vs.AA:OR 3.58-95 GG vs.AA:OR 1.31-9.83 fix model;GA vs.AA:OR 1.8095 I: 0.86-3.75 fix model;GG GA vs.AA:OR 2.14 95 CI1.07-4.27 fix model; G vs.A:OR 1.86 / 95 CIQ: 1.16-2.98 model; does not contain the results of the PCV group: GG vs.AA:OR 1.55 95 CI 0.87-2.74 I fix model;GA vs.AA:OR 1.6595 CI: 0.64-4.25random model; GG GA vs.AA:OR 1.63 95 I: 0.75-3.53 random model;G vs.A:OR 1.34 95 I: 1.01-1.78 model; Caucasians have no statistical difference. Conclusion: the polymorphism of rs11200638 locus of HTRA1 gene is associated with the therapeutic response to wet AMD in East Asian population. The patients carrying wild type allele G indicates a high response rate and a low response rate of A allele carrying mutant gene, especially for PCV subtype. This phenomenon is more obvious. No statistical significance was found in Caucasian population. Therefore, HTRA1 gene may become a gene marker for individual treatment of wet AMD and obtain the best vision effect, but more high-quality and large sample studies are needed to further verify it.
【学位授予单位】：河南科技大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R774.5

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