血管内皮生长因子-2578C/A基因的多态性与糖尿病视网膜病变发生风险的Meta分析

Meta analysis of the association between vascular endothelial growth factor-2578C/A polymorphism and risk for diabetic retinopathy

背景 研究表明血管内皮生长因子（VEGF）在糖尿病视网膜病变（DR）的发生和发展中发挥重要作用,目前VEGF-2578 C/A基因多态性与DR发病风险的关联性是一个研究热点. 目的 明确VEGF-2578C/A基因多态性在不同种族人群中引起DR的风险. 方法 按照检索策略,用计算机检索的方法检索PubMed、Cochrane Library、EMbase、万方科技期刊全文数据库、清华CNKI数据库、重庆维普中文科技期刊全文数据库,最后检索日期为2014年4月,对筛选VEGF-2578C/A与DR相关的病例-对照研究文献进行Meta分析,分析指标包括VEGF-2578C等位基因与DR的关联性、VEGF-2578C/A基因多态性与DR的关联性、欧洲人VEGF-2578A等位基因与DR的关联性分析,并对纳入文献的发表偏倚进行敏感性分析.采用RevMan 5.0软件进行定量分析,所有研究的合并优势比（OR）和95％可信区间（CI）.结果 共筛选出8篇病例-对照研究文献共9组数据,包括DR组1228例和糖尿病无视网膜病变（DWR）组1 224例.VEGF-2578C/A与DR有关联,其A等位基因及AA基因型为DR的危险基因A与C：OR=1.39,95％ CI：1.08～1.800,Z=2.52,P=0.01;AA与CC＋C/A：OR=1.53,95％ CI：1.05 ～ 2.24,Z=2.20,P=0.03;CC与AA＋C/A：OR=0.70,95％ CI：0.50～0.98,Z=2.10,P=0.04）;将非Hardy-Weinberg遗传平衡的研究纳入进行敏感性分析,其结果不受影响（A与C：OR=1.35,95％ CI：1.09 ～ 1.67,Z=2.74,P=0.006）;欧洲人VEGF-2578 C/A与DR相关联,且其A等位基因为其危险基因（OR=1.50,95％ CI：1.02～2.21,Z=2.07,P=0.04）,但VEGF-2578AA及CC基因型与DR无明显关联（P＞0.05）;亚洲人VEGF-2578C/A与DR无明显关联（P＞0.05）.各研究未发现明显发表偏倚.结论 欧洲人VEGF-2578C/A与DR相关联,且其A等位基因为其危险因素,而亚洲人未发现VEGF-2578C/A与DR相关联.仍需来自不同人种的大样本量相关研究.

Background Studies showed that vascular endothelial growth factor （VEGF） plays an important role in the development and progress of diabetic retinopathy （DR）,and the association between VEGF-2578C/A polymorphism（SNPs） and risk for DR is a hotspot.Objective This Meta analysis aimed to investigate the comprehensive and reliable conclusion in the association of VEGF-2578C/A SNPs and risk for DR in different races.Methods A systematic search of electronic databases including PubMed,Cochrane Library,EMbase,VIP,Wanfang technological,CNKI and reference lists of relevant articles was carried out until April,2014.Case-control studies on the relationship between VEGF-2578C/A SNPs and DR were selected based on inclusion and exclusion criteria,and the relevance of VEGF-2578C allele to DR,the relevance of VEGF-2578C/A SNPs to DR and the relevance of VEGF-2578A allele to Caucasian DR were quantitatively analyzed.Begger funnel plot of publication biases on the relationships of VEGF SNPs with the risk of DR under the allele and dominant models was drown.RevMan 5.0 software was used for the statistical analysis.The pooled odds ratio （OR） and corresponding 95% confidence interval （CI） were used to assess the strength of the association.Results A total of 1 228 DR cases and 1 224 diabetes controls without retinopathy（DWR） were included from 8 independent studies （9 groups of data）.A significant relationships between VEGF-2578A allelic gene and VEGF-2578AA gene type with DR were found in all samples,and the A allelic gene and AA gene type were the risk genes of DR （A versus C：OR=1.39,95% CI=1.08-1.80,Z=2.52,P=0.01;AA versus CC＋C/A：OR=1.53,95% CI=1.05-2.24,Z=2.20,P=0.03;CC versus AA＋C/A：OR=0.70,95% CI=0.50-0.98,Z =2.10,P =0.04）.When the other two studies which did not meet the HardyWeinberg Equilibrium were incorporated in a sensitivity analysis,the results were not materially altered.VEGF-2578 A allelic gene was the risk gene to Europeans with DR （OR =1.50,95% CI=1.02-2.21,Z =2.07,P =0.04）,but not among Asians in subgroup analysis （P〉0.05）.No significant publication bias was found.Conclusions The Meta analysis demonstrates that VEGF-2578C/A is associated with DR in Europeans but not in Asians.Further case-control studies based on larger sample size are still needed,especially in Asians.