血管内皮生长因子基因启动子区多态与散发性阿尔茨海默病的关系

Association between promoter variations of vascular endothelial growth factor gene and sporadic Alzhehner＇s disease

目的研究血管内皮生长因子（vascular endothelial growth factor，VEGF）基因启动子区多态与散发性阿尔茨海默病（sporadic Alzheimer’s disease，SAD）发病的关系。方法用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）或直接测序的方法对北方汉族279例SAD患者和317名健康对照者进行多态分型。采用SPSS11．5统计学软件包进行等位基因和基因型分布的比较及其与疾病的关联分析。结果北方汉族人群中VEGF启动子存在3个多态位点：-2578C／A（rs699947）、-2549I／D（rs35569394）和-1154G／A（rs1570360），其中-2549I／D位点为18个碱基的插入或缺失。-2578C／A和-2549I／D存在显著的连锁不平衡，当-2578为A等位基因时，-2549I／D位点有18个碱基的插入，而当-2578是C纯合子时，-2549I／D位点则为18个碱基的缺失。这3个多态位点的基因型频率、等位基因频率以及单体型分布在SAD患者和对照组间差异无统计学意义。用Logistic回归校正年龄、性别和ApoE状态后，-1154G／A的GG基因型增加了SAD的发病风险。在不携带ApoEs4的亚组中，单体型-2549D／-1154G可能增加SAD的发病风险（OR=1．325，95％CI 1．023～1．716，P=0．033）。结论北方汉族人群中VEGF启动子存在3个多态位点-2578C／A、-2549I／D和-1154G／A。-1154G／A的GG基因型增加了SAD的发病风险。在不携带APOE ε4的情况下，VEGF启动子的-2549D／-1154G单体型可能是SAD发病的危险因素。

Objective To investigate the correlation of the vascular endothelial growth factor （VEGF） gene variations in the promoter region with the sporadic Alzheimer＇s disease （SAD） in Chinese Han population for better understanding the mechanism of SAD. Methods The polymorphisms of 279 SAD Chinese Han patients from Northern China were analyzed by comparing with those from 317 healthy individuals using the method of polymerase chain reaction-restriction fragment length polymorphism （ PCR- RFLP） or direct sequencing. The commercial statistics package SPSS 11.5 was used to compare the distribution of the allele and the genotype, and to analyze their correlations with SAD. Results Three polymorphism sites were found for the VEGF promoters in the Chinese Han sample group including -2578C/A, - 2549I/D and - 1154G/A. - 2549I/D and - 2578C/A exhibiting strong linkage disequilibrium. Individuals with the A allele at position -2578 had an insertion of 18 nucleotides at -2459I/D, whereas CC homozygotes did not contain this insertion at -2459I/D. No significant differences were found between the SAD patients and the controls in the 3 VEGF polymorphisms. After adjusting the data for gender, age and the ApoE e4 allele using Logistic regression, the - 1154G/G genotype of the VEGF promoter might increase the risk of SAD in Chinese Han population. Among the subgroup without the ApoE ε4 allele, -2549D/- 1154G haplotype might increase the risk for SAD （OR = 1. 325, 95% CI 1. 023--1. 716, P = 0. 033 ）. Conclusions Three polymorphism sites （ - 2578C/A, - 2549I/D, and - 1154G/A） are found in the VEGF promoter regions in Chinese Han population. The - 1154G/G genotype of the VEGF promote appears to increase the risk of SAD in Chinese Han population. In the absence of ApoE ε4, the -2549D/- 1154G haplotype of the VEGF promoter appears to affect the risk for SAD.