血管内皮生长因子基因与习惯性流产的相关性
The association between the vascular endothelial growth factor gene and recurrent spontaneous abortion

摘要：目的 探讨血管内皮生长因子(vascular endothelial growth factor, VEGF)基因10个单核苷酸多态性(single nucleotide polymorphism, SNP)位点与习惯性流产的相关性。方法 严格按照诊断标准，选取无亲缘关系的习惯性流产患者241名(习惯性流产组)及健康体检者265名(正常对照组)；采取静脉血，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检测10个SNP的基因型；采用SPSS11.5及Haploview 4.2软件统计分析基因型、等位基因及单倍型频率在病例组和对照组中的差异。结果 VEGF基因rs3025020(内含子6)及rs3025039(3′非翻译区)基因型及等位基因频率分布在习惯性流产组和正常对照组中的差异有统计学意义(P<0.05)。习惯性流产组rs3025020位点T等位基因频率显著高于正常对照组(P=0.0002，OR=1.620，95% CI=1.260～2.084)；习惯性流产组rs3025039位点T等位基因频率显著高于正常对照组(P=0.001，OR=1.628, 95% CI =1.209～2.192)。连锁不平衡分析发现4个单倍型高度连锁(D′>0.9)。习惯性流产组A-C单倍型(rs833069-rs3024998)频率显著低于正常对照组(P=0.034)；习惯性流产组T-G-C单倍型(rs3025020-rs3025030-rs3025039)频率显著低于正常对照组(P=0.032)；习惯性流产组C-G-C单倍型(rs3025020-rs3025030-rs3025039)频率显著高于正常对照组(P=0.0002)。结论 VEGF基因rs3025020、rs3025039位点可能与习惯性流产有关，携带有C-G-C单倍型(rs3025020-rs3025030-rs3025039)的个体可能更容易患习惯性流产。
ABSTRACT: Objective To evaluate the association between 10 single nucleotide polymorphisms (SNP) of the vascular endothelial growth factor (VEGF) gene and the risk of recurrent spontaneous abortion (RSA). Methods We examined the potential association between RSA and 10 SNPs of the VEGF gene using the MassARRAY system. The participants enrolled in this study included 241 patients with RSA and 265 healthy women as the healthy controls from a Chinese Han population. SPSS11.5 and Haploview 4.2 were employed. Results The results showed that rs3025020 (6 introns) and rs3025039 (3’UTR) were significantly associated with RSA (P<0.05). More frequency of rs3025020 T allele (P=0.0002, OR=1.620, 95% CI=1.260-2.084) and rs3025039 T allele (P=0.001, OR=1.628, 95% CI= 1.209-2.192) were found in RSA subjects. Furthermore, strong linkage disequilibrium (LD) was observed in 4 locks (D’>0.9). The significantly more A-C (rs833069-rs3024998) haplotypes were found in the controls (P=0.034). The significantly more T-G-C (rs3025020-rs3025030-rs3025039) haplotypes were found in the controls (P=0.032). The significantly more C-G-C (rs3025020-rs3025030-rs3025039) haplotypes were found in the RSA subjects (P=0.0002). Conclusion These findings suggest the role of VEGF gene polymorphisms (rs3025020 and rs3025039) in RSA of a Chinese Han population. Individuals with C-G-C (rs3025020-rs3025030-rs3025039) haplotypes may be at risk for RSA