血管内皮生长因子基因多态性与陕西汉族阿尔茨海默病的相关性研究
Association between single-nucleotide polymorphisms of vascular endothelial growth factor gene and Alzheimer’s disease in Shaanxi Han population

摘要：目的 旨在探讨血管内皮生长因子(vascular endothelial growth factor, VEGF)基因8个单核苷酸多态性(single-nucleotide polymorphism, SNP)位点与陕西汉族阿尔茨海默病(Alzheimer disease, AD)的相关性。方法 选取陕西汉族AD患者214名(疾病组)及健康体检者(对照组)249名提取基因组DNA，采用基质辅助激光解吸电离飞行时间质谱技术对9个SNP的基因型进行分型，采用SPSS 16.0及Haploview 4.2软件统计分析各基因型、等位基因及单倍型频率在病例组及对照组中的差异。结果 VEGF基因rs3025039(3’非翻译区)基因型及等位基因频率分布在AD组及正常对照组差异有统计学意义(P<0.05)。AD组T等位基因频率显著高于正常对照组(P=0.008，OR=1.527, 95% CI=1.116～2.088)。连锁不平衡分析发现2个单倍型高度连锁(单倍型1：rs699947-rs1570360-rs2010963；单倍型2：rs3024997-rs3024998-rs3025006)(D’>0.9)。然而，其单倍型频率在AD组及正常对照组均无统计学差异(P>0.05)。结论 VEGF基因功能区rs3025039位点可能与AD有关，携带有rs3025039 T等位基因的个体可能更容易患AD。
ABSTRACT: Objective To evaluate the association between 8 single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) gene and the risk of Alzheimer’s disease (AD) in Shaanxi Han population. Methods We examined the potential association between AD and 8 SNPs of VEGF gene using the MassARRAY system. The participants enrolled in this study included 214 patients with AD and 249 healthy controls from Shaanxi Han population. SPSS16.0 and Haploview 4.2 were employed to analyze differences in genotypes, alleles and haplotypes between the two groups. Results The results showed that rs3025039 (3’UTR) were significantly associated with AD (P<0.05). Greater frequency of rs3025039 T allele (P=0.008, OR=1.527, 95% CI=1.116-2.088) was found in AD subjects. Furthermore, strong linkage disequilibrium (LD) was observed in 2 locks (block1: rs699947-rs1570360-rs2010963; block 2: rs3024997-rs3024998-rs3025006) (D’>0.9). There were no significant haplotypes in block 1 and block 2 (P=0.034) found between the patients and controls. Conclusion These findings point to the role for VEGF gene polymorphisms (rs3025039) in AD of a Shaanxi Han population. Individuals with T allele of rs3025039 may be at a higher risk for AD