【摘要】：目的:用Meta分析法對HTRA1基因rs11200638位點多態(tài)性(SNP)與濕性年齡相關(guān)性黃斑變性(AMD)抗新生血管治療無應(yīng)答的相關(guān)性進行系統(tǒng)評價。方法:計算機檢索Pubmed、Embase及Cochrane圖書館等電子數(shù)據(jù)庫,納入治療新生血管性AMD及PCV的隊列研究。治療方式包括抗新生血管藥物治療(雷珠單抗/貝伐單抗)或/和光動力治療。以治療應(yīng)答人數(shù)與無應(yīng)答人數(shù)的比值比(OR)和95%置信區(qū)間(CI)作為效應(yīng)指標,采用Rev Man 5.3版軟件進行Meta分析,利用固定效應(yīng)模型或隨機效應(yīng)模型進行評估,運用Q檢驗評估研究異質(zhì)性,采用NOS量表對文獻質(zhì)量進行評價。結(jié)果:最終納入9篇病例對照研究,共2096例病例,整體人群Meta分析結(jié)果顯示:SNP rs11200638基因多態(tài)性與濕性AMD抗新生血管治療應(yīng)答有相關(guān)性,攜帶基因型GG或GA的治療應(yīng)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)。針對不同人群進行亞組分析顯示:東亞人群中,攜帶野生型等位基因G應(yīng)答率高于突變型等位基因A,野生純合基因型GG和野生雜合基因型GA應(yīng)答率高于突變純合基因型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,等位基因之間及各基因型之間治療應(yīng)答率無統(tǒng)計學差異。以臨床類型不同進行亞組分析顯示:在東亞人群含PCV患者組中,各基因?qū)Ρ冉M效應(yīng)值OR均大于不含PCV組。含PCV組結(jié)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組結(jié)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;高加索人群無統(tǒng)計學差異。結(jié)論:HTRA1基因rs11200638位點多態(tài)性與東亞人群濕性AMD的治療應(yīng)答具有相關(guān)性,患者攜帶野生型等位基因G預(yù)示治療應(yīng)答率高,攜帶突變型等位基因A應(yīng)答率低,尤其對于PCV亞型,此現(xiàn)象更明顯。在高加索人群未發(fā)現(xiàn)統(tǒng)計學意義。因此,HTRA1基因有可能成為濕性AMD實現(xiàn)個體化治療并獲取最佳視力效果的基因標記物,但仍需更多的高質(zhì)量大樣本研究進一步驗證。
[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.
【學位授予單位】：河南科技大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R774.5

【參考文獻】

相關(guān)期刊論文 前9條

1 Fernando Cruz-Gonzalez;Lucia Cabrillo-Estevez;Vanesa Rivero-Gutierrez;Ana Sanchez-Jara;Lourdes De Juan-Marcos;Rogelio Gonzalez-Sarmiento;;Influence of CFH,HTRA1 and ARMS2 polymorphisms in the response to intravitreal ranibizumab treatment for wet age-related macular degeneration in a Spanish population[J];International Journal of Ophthalmology;2016年09期

2 楊景元;王爾茜;陳有信;;光動力療法與玻璃體腔注射抗血管內(nèi)皮生長因子制劑治療息肉樣脈絡(luò)膜血管病變的meta分析[J];中華眼底病雜志;2016年01期

3 周佳;陸瓊;;抗血管內(nèi)皮生長因子聯(lián)合光動力療法治療黃斑變性的系統(tǒng)分析[J];上海交通大學學報(醫(yī)學版);2012年12期

4 劉冉;丁小燕;;息肉樣脈絡(luò)膜血管病變與滲出型老年性黃斑變性的異同[J];中華眼底病雜志;2012年05期

5 韓建文;張學軍;;全基因組關(guān)聯(lián)研究現(xiàn)狀[J];遺傳;2011年01期

6 王淑新;連林生;;單核苷酸多態(tài)性作為新一代分子標記的優(yōu)越性[J];中國畜牧獸醫(yī);2008年04期

7 侯慧媛,王雨生;血管內(nèi)皮生長因子誘發(fā)脈絡(luò)膜新生血管的分子機制[J];中華眼底病雜志;2005年06期

8 鄒海東,張fs,許迅,汪楓樺,張世杰;上海市靜安區(qū)曹家渡街道年齡相關(guān)性黃斑變性的患病率調(diào)查[J];中華眼科雜志;2005年01期

9 吳昕彥,張慶華,陳竺;單核苷酸多態(tài)性研究及應(yīng)用[J];中華醫(yī)學遺傳學雜志;2000年01期

，

本文編號：2335868