University of Kansas, Lawrence, KS, USA.
Mol Biol Rep. 2011 Apr;38(4):2417-25. doi: 10.1007/s11033-010-0376-8. Epub 2010 Nov 16.
The aim of this study was to determine the association between hypertensive nephropathy and gene polymorphisms of vascular endothelial growth factor (VEGF) in a self-reported Hispanic patient group. A total of 155 Hispanic living kidney donors as controls and a total of 86 Hispanic kidney transplant patients, whose renal failure was attributed to hypertensive nephropathy after ruling out diabetes mellitus or other causes, were genotyped for four different single nucleotide polymorphisms of VEGF: -2578 C>A (rs699947), -1154 G>A (rs1570360), -460 C>T (rs833061), and +936 C>T (rs3025039). The homozygous mutant type (AA) of VEGF -1154 G>A (rs1570360) was found with significantly higher frequency in the hypertensive nephropathy patients than in controls. On the other hand, homozygous wild type (GG) was found less frequently in the hypertensive nephropathy patient group than in the control group. Linkage disequilibrium (LD) analyses revealed a high degree of LD among VEGF -2578 C>A (rs699947), VEGF -1154 G>A (rs1570360), and VEGF -460 C>T (rs833061). The haplotype analysis revealed that two haplotypes, CGTC and CATC (in the order of VEGF -2578 C>A (rs699947), -1154 G>A (1570360), -460 C>T (rs833061), and +936 C>T (3025039)), were significantly associated with hypertensive nephropathy in Hispanic patients. Hence, the -1154 G>A polymorphism (rs1570360) and two haplotypes (CGTC and CATC) of VEGF appear to be associated with hypertensive nephropathy in Hispanic patients who developed end-stage renal disease requiring kidney transplant.
本研究旨在确定血管内皮生长因子 (VEGF) 基因多态性与高血压性肾病在自报西班牙裔患者群体中的关联。共有 155 名西班牙裔活体供肾者作为对照，共有 86 名西班牙裔肾移植患者，这些患者的肾衰竭归因于高血压性肾病，排除糖尿病或其他原因后，对 VEGF 的四个不同单核苷酸多态性进行基因分型：-2578 C>A(rs699947)、-1154 G>A(rs1570360)、-460 C>T(rs833061)和+936 C>T(rs3025039)。在高血压性肾病患者中，VEGF-1154 G>A(rs1570360)的纯合突变型 (AA) 频率明显高于对照组。另一方面，高血压性肾病患者组中纯合野生型 (GG) 的频率明显低于对照组。连锁不平衡 (LD) 分析显示 VEGF-2578 C>A(rs699947)、VEGF-1154 G>A(rs1570360)和 VEGF-460 C>T(rs833061)之间存在高度 LD。单体型分析显示，两个单体型 CGTC 和 CATC(按 VEGF-2578 C>A(rs699947)、-1154 G>A(rs1570360)、-460 C>T(rs833061)和+936 C>T(rs3025039)的顺序)与西班牙裔患者的高血压性肾病显著相关。因此，VEGF 的-1154 G>A 多态性(rs1570360)和两个单体型 (CGTC 和 CATC) 似乎与发生需要肾移植的终末期肾病的西班牙裔患者的高血压性肾病有关。
