血管内皮生长因子的936C／T基因多态性与年龄相关性黄斑变性的关联研究

Association between vascular endothelial growth factor ＋ 936C/T gene polymorphism and age-related macular degeneration

背景研究表明，血管内皮生长因子（VEGF）与年龄相关性黄斑变性（AMD）的发病过程密切相关，是治疗湿性AMD时的靶因子，但其确切的发病机制尚未完全明确。VEGF基因多态性与AMD之间的关系正在成为新的研究热点，但中国汉族人群中相关的研究尚少。目的研究VEGF＋936C／T基因多态性与中国人AMD发生的关系。方法采用前瞻性非随机对照研究设计，研究流程遵循赫尔辛基宣言。收集2009年1月至2012年1月就诊于解放军第二炮兵总医院眼科的AMD患者200例，同期选取健康志愿者200名作为正常对照组，年龄和性别与AMD患者均相匹配。采集所有受检者空腹静脉血5m1提取基因组DNA，采用限制性内切酶片段长度多态性分析（RFLP）法分析受检者VEGF＋936C／T基因在启动子区与3’非翻译区的多态性，比较两组受检者陋GF＋936c／T基因型出现的频率，分析VEGF＋936C／T基因多态性与AMD发病的危险度。结果AMD组与正常对照组间受检者吸烟情况（P=0．76）、高血压（P=0．84）、高血脂（P=0．71）、糖尿病（P=0．86）或心血管系统疾病（P=0．89）的频数和构成比的差异均无统计学意义，两组间受检者体质量指数（BMI）的差异无统计学意义（P=0．18）。200例AMD患者中，18例表现为TT基因型，占9．0％；而正常对照组该基因型7例，占3．5％，差异有统计学意义（P=0．03），95％可信区间（CI）的比值比（OR）为2．73。两组间受检者CC、CT基因型频率的差异均无统计学意义（P=0．52、0．57）；两组之间基因型与等位基因频率符合Hardy—Weinberg平衡。早期AMD、地图状萎缩、脉络膜新生血管型AMD之间受检者CC、CT、TT基因型频率的差异均无统计学意义（P〉0．05）。结论中国汉族人群VEGF＋936TT基因型的基因多态性与AMD发病相关。

Background Vascular endothelial growth factor （VEGF）has been shown to be associated with the pathogenesis of age-related maeular degeneration （AMD） , therefore VEGF is a target for the treatment of wet AMD. However, the mechanism of VEGF in the pathogenesis of AMD is not clearly understood. Studying the correlation between VEGF gene polymorphism and AMD is becoming a new research hotspot, but relevant studies on Han Chinese have not been performed. Objective This study was to investigate the association between the VEGF ＋936C/T gene polymorphism and AMD in the Chinese population. Methods A pilot prospective and non- randomized controlled trial was designed. This protocol complied with Declaration of Helsinki and was approved by the Ethic Committee of Chinese PLA Second Artillery General Hospital. Written informed consent was obtained from each subject prior to entering the study. Two hundred AMD patients and 200 age-and gender-matched normal controls were enrolled in this study. The genomic DNA was extracted from the peripheral blood samples of the subjects,and analysis of the VEGF polymorphisms at the ＋936 position in the promoter and 3＂-untranslated regions was performed by the restriction fragment length polymorphism method. Frequencies of the VEGF＋936C/T genotype were compared between the two groups, and the risk of the VEGF＋ 936C/T gene polymorphism in pre-disposing AMD was evaluated. Results No significant differences were seen in the incidence rates of smoking（ P = 0. 76） , hypertension（ P = 0.84） , hyperlipidemia （ P = 0.71 ） , diabetes mellitus （ P = 0.86 ） and cardiovascular disease （ P = 0. 89 ） between the AM D group and the normal control group,and BMI was matched between the two groups （P = 0.18 ）. The prevalence of the TT genotype was 9.0% （18/200）in the AMD group, but that in the normal control was 3.5% （7/200）, showing a significant difference between the two groups （ P = 0.03 ）. The odds ratio （OR） was 2.73 with a 95% confidence interval（Cl） of 1.11 to 6.68 for AMD in this genotype. The CC and CT genotypes were not significantly different between the two groups （P = 0.52, P = 0.57 ）. The genotype frequency and allele frequency conformed to Hardy- Weinberg equilibrium law. There were no significant differences found in the CC,CT,TT genotype frequencies among the early AMD,geographic atrophy AMD and choroidal neovascular AMD （ all at P〉0.05 ）. Conclusions The VEGF＋936TT genotype is associated with AMD in Han Chinese population.