血管内皮细胞功能相关基因多态性与子痫前期的遗传易感性研究
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摘要
目的探讨血管内皮细胞功能相关基因即内皮型一氧化氮合成酶(eNOS/NOS3)、血管内皮生长因子(VEGF)、胰岛素样生长因子(IGF1)基因的单核苷酸多态性(SNP)与子痫前期(PE)发病的相关性。方法选取2014年7月至2015年5月于南方医科大学附属深圳妇幼保健院分娩的汉族妇女442例,采用SNapshot技术对eNOS、VEGF、IGF基因5个位点进行检测,分析两组间基因型及等位基因频率的差异。结果 (1)深圳地区汉族妇女中暂未发现存在IGF1基因rs5742620位点、NOS3基因27bp-VNTR in intron 4位点的多态性。(2)PE组NOS3基因rs2070744位点AA基因型、A等位基因频率明显低于对照组(95.5%vs99.3%,P=0.007,OR=0.14,95%CI为0.03-0.73;97.4%vs99.7%,P=0.003,OR=0.13,95%CI为0.028-0.632)。(3)PE与对照组比较,NOS3基因rs1799983位点GG、GT、TT基因型及等位基因分布无显著差异;VEGF基因rs3025039位点GG、AG、AA基因型及等位基因分布无显著差异。结论 (1)NOS3基因rs2070744位点可能与深圳地区汉族妇女PE发生有关。(2)NOS3基因rs2070744位点AA基因型、A等位基因可能是本群体PE发病的保护因素。(3)IGF1基因rs5742620位点、NOS3基因27bp-VNTR in intron 4位点为本群体的罕见突变。
引文
[1]周璐,等.基于多因子降维法的子痫前期易感基因-基因交互作用研究[J].现代妇产科进展,2018,1:1-5.
[2]Smith-Jackson K,et al. Placental expression of eNOS,iNOS and the major protein components of caveolae in women with preeclampsia[J].Placenta,2015,36(5):607-10.
[3]Du L,et al.eNOS/iNOS and endoplasmic reticulum stress-induced apoptosis in the placentas of patients with preeclampsia[J].J Hum Hypertens,2017,31(1):49-55.
[4]Ben Ali Gannoun M,et al. Association of common eNOS/NOS3polymorphisms with preeclampsia in Tunisian Arabs[J].Gene,2015,569(2):303-7.
[5]Ben Ali,Gannoun M,et al. Vascular endothelial growth factor single nucleotide polymorphisms and haplotypes in pre-eclampsia:A case-control study[J].Cytokine,2017,97:175-180.
[6]Silva VR,et al. Investigation of polymorphisms in pre-eclampsia related genes VEGF and IL1A[J].Arch Gynecol Obstet,2015,291(5):1029-35.
[7]Mahmoud S,et al. Maternal and umbilical cord blood level of macrophage migration inhibitory factor and insulin like growth factor in Sudanese women with preeclampsia[J].J Obstet Gynaecol,2018.1-5.
[8]张战红,等.eNOS基因和MTHFR基因多态性与子痫前期发病关系的研究[J].中国优生与遗传杂志,2007,11:21-23+15.
[9]邓婕,等.ACE、AT_1R、eNOS基因多态性与重度子痫前期的相关性[J].中国妇幼保健,2010,25(35):5277-5279.
[10]苏念军,等.广东籍汉族妇女N5,10-MTHFR基因和eNOS基因多态性与子痫前期和子痫相关性的研究[J].现代妇产科进展,2011,20(3):199-202.
[11] Sakar MN,et al. Association of endothelial nitric oxide synthase gene G894T polymorphism and serum nitric oxide levels in patients with preeclampsia and gestational hypertension[J].J Matern Fetal Neonatal Med,2015,28(16):1907-11.
[12] Aggarwal S,et al.Preeclampsia in North Indian women:the contribution of genetic polymorphisms[J].J Obstet Gynaecol Res,2011,37(10):1335-41.
[13]张竑卉,何云,张彩媚.血管内皮生长因子单核苷酸多态性与子痫前期易感性的相关研究[J].现代医学,2014,42(4):327-331.
[14]陈宝丽,等.血管内皮生长因子基因多态性与重度子痫前期易感性[J].中国妇幼保健,2011,26(32):5052-5055.
[15]黄余良,刘珏. VEGF基因多态性与子痫前期易感性的研究[J].中国妇幼保健,2009,24(19):2712-2714.
[2]Smith-Jackson K,et al. Placental expression of eNOS,iNOS and the major protein components of caveolae in women with preeclampsia[J].Placenta,2015,36(5):607-10.
[3]Du L,et al.eNOS/iNOS and endoplasmic reticulum stress-induced apoptosis in the placentas of patients with preeclampsia[J].J Hum Hypertens,2017,31(1):49-55.
[4]Ben Ali Gannoun M,et al. Association of common eNOS/NOS3polymorphisms with preeclampsia in Tunisian Arabs[J].Gene,2015,569(2):303-7.
[5]Ben Ali,Gannoun M,et al. Vascular endothelial growth factor single nucleotide polymorphisms and haplotypes in pre-eclampsia:A case-control study[J].Cytokine,2017,97:175-180.
[6]Silva VR,et al. Investigation of polymorphisms in pre-eclampsia related genes VEGF and IL1A[J].Arch Gynecol Obstet,2015,291(5):1029-35.
[7]Mahmoud S,et al. Maternal and umbilical cord blood level of macrophage migration inhibitory factor and insulin like growth factor in Sudanese women with preeclampsia[J].J Obstet Gynaecol,2018.1-5.
[8]张战红,等.eNOS基因和MTHFR基因多态性与子痫前期发病关系的研究[J].中国优生与遗传杂志,2007,11:21-23+15.
[9]邓婕,等.ACE、AT_1R、eNOS基因多态性与重度子痫前期的相关性[J].中国妇幼保健,2010,25(35):5277-5279.
[10]苏念军,等.广东籍汉族妇女N5,10-MTHFR基因和eNOS基因多态性与子痫前期和子痫相关性的研究[J].现代妇产科进展,2011,20(3):199-202.
[11] Sakar MN,et al. Association of endothelial nitric oxide synthase gene G894T polymorphism and serum nitric oxide levels in patients with preeclampsia and gestational hypertension[J].J Matern Fetal Neonatal Med,2015,28(16):1907-11.
[12] Aggarwal S,et al.Preeclampsia in North Indian women:the contribution of genetic polymorphisms[J].J Obstet Gynaecol Res,2011,37(10):1335-41.
[13]张竑卉,何云,张彩媚.血管内皮生长因子单核苷酸多态性与子痫前期易感性的相关研究[J].现代医学,2014,42(4):327-331.
[14]陈宝丽,等.血管内皮生长因子基因多态性与重度子痫前期易感性[J].中国妇幼保健,2011,26(32):5052-5055.
[15]黄余良,刘珏. VEGF基因多态性与子痫前期易感性的研究[J].中国妇幼保健,2009,24(19):2712-2714.