血管内皮生长因子基因多态性与异位妊娠的关联研究

Association of vascular endothelial growth factor gene polymorphisms with ectopic pregnancy among Chinesewomen

目的探讨血管内皮生长因子（vascularendothelialgrowthfactor，VEGF）基因单核苷酸多态性（singlenucleotidepolymorphism，SNP）与异位妊娠发病风险的关系。方法应用聚合酶链反应-限制性片段长度多态性（polymerasechainreaction—restrictionfragmentlengthpolymorphism，PCR-RFLP）方法对192例异位妊娠患者和210名健康绝经后女性VEGF-460c／T、-1154G／A、-2578C／A、＋936C／T4个SNP位点进行基因分型。结果VEGF-460C／T和＋936C／T位点基因型及等位基因频率分布在病例组和对照组间的差异无统计学意义（P〉0．05）。与GG基因型相比，携带VEGF-1154G／A位点A等位基因（GA＋AA基因型）可显著降低异位妊娠的发病风险（0R-0．61，95％CI：0．42～O．87）。与CC基因型相比，携带VEGF-2578C／A位点A等位基因（AA＋CA基因型）可显著降低异位妊娠的发病风险（OR-0．66，95％CI：0．44～O．99）。与T—GC单倍型相比，T—A—A和C-A-A单倍型均可明显降低异位妊娠的发病风险（P-0．020，OR-0．4l，95％CI：0．19～0．89；P-0．014，OR-0．29，95％Cf：0．11～0．82）。结论携带VEGF-1154G／A和-2578C／A多态的A等位基因可能显著降低异位妊娠的发病风险，提示该等位基因可能是异位妊娠发病的-个潜在的保护因素VEGF-460C／T、-1154G／A和-2578C／A3个多态位点间存在部分连锁不平衡现象，T-A—A和C-小A单倍型均可明显降低异位妊娠的发病风险。

Objective To assess the association of vascular endothelial growth factor （VEGF） gene polymorphisms with ectopic pregnancy （EP） among Chinese women. Methods A case-control study was carried out, which compared 192 women with a history of EP with 210 post-menopausal controls who had two pregnancies but no history of EP for the genotypes of the VEGF gene. Polymorphisms of the VEGF gene including --460C/T, --l154G/A, --2578C/A and d-936C/T were determined with a polymerase chain reaction-restriction fragment length polymorphism method. Results No significant difference was found in the genotypie and allelic distribution of the --460C/T and -k 936C/T polymorphisms between the two groups. Compared with the GG genotype, the VEGF --1154 AAq-GA genotype could significantly decrease the risk of EP （OR=O. 61, 95%CI： 0. 42-0. 87）. Compared with the CC genotype, VEGF --2578 AA＋CA genotype could significantly reduce the risk of EP （OR=O. 66, 95%CI..0.44-0.99）. Haplotype analysis suggested that the T-A-A （VEGF --460/--1154/--2578） and C-A-A haplotypes could significantly decrease the risk of EP compared with the T-G-C haplotype （P=0. 020, OR=O. 41, 95%CI..0. 19-0.89;P =0. 014,OR=0.29,95%CI..0.11-0.82）. Conclusion The --1154A or --2578A alleles of the VEGF gene can significantly decrease the risk of EP among Chinese women. The VEGF --460C/T, --1154G/A and -- 2578C/A polymorphisms showed a linkage disequilibrium. Both T-A-A and C-A-A haplotypes can significantly decrease the risk of EP.