Epistasis among eNOS, MMP-9 and VEGF maternal genotypes in hypertensive disorders of pregnancy
Epistasis among eNOS, MMP-9 and VEGF maternal genotypes in hypertensive disorders of pregnancy
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DOI：
10.1038/hr.2012.60
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发表时间：
2012-09-01
影响因子：
5.4
通讯作者：
Tanus-Santos, Jose E.
中科院分区：
文献类型：
--
作者：
Luizon, Marcelo R.;Sandrim, Valeria C.;Tanus-Santos, Jose E.
内皮型一氧化氮合酶（eNOS）、基质金属蛋白酶-9（MMP-9）和血管内皮生长因子（VEGF）基因多态性与妊娠期高血压疾病相关。然而，上位性被认为是先兆子痫（PE）遗传易感性的重要组成部分。本研究的目的是描述这些基因在PE和妊娠期高血压（GH）中的相互作用。eNOS的七种临床相关多态性（T-786 C，rs 2070744，内含子4中可变数目的串联重复序列和Glu 298 Asp，rs 1799983），MMP-9（C-1562 T，rs3918242和-90（CA）（13-25），rs 2234681）和VEGF在122例PE患者中，通过TaqMan等位基因鉴别试验或PCR和电泳分离片段对C-2578 A，rs699947和G-634 C，rs 2010963进行基因分型，107例GH患者和102例正常血压妊娠（NP）妇女作为对照组。一个强大的多因素降维分析用于表征基因-基因相互作用。虽然在GH组和NP组之间没有观察到显著的基因型组合（P>0.05），但MMP-9- 1562 CC和VEGF-634 GG的组合在NP组中比PE组更常见（P
Polymorphisms of the endothelial nitric oxide synthase (eNOS), matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) genes were shown to be associated with hypertensive disorders of pregnancy. However, epistasis is suggested to be an important component of the genetic susceptibility to preeclampsia (PE). The aim of this study was to characterize the interactions among these genes in PE and gestational hypertension (GH). Seven clinically relevant polymorphisms of eNOS (T-786C, rs2070744, a variable number of tandem repeats in intron 4 and Glu298Asp, rs1799983), MMP-9 (C-1562T, rs3918242 and -90(CA)(13-25), rs2234681) and VEGF (C-2578A, rs699947 and G-634C, rs2010963) were genotyped by TaqMan allelic discrimination assays or PCR and fragment separation by electrophoresis in 122 patients with PE, 107 patients with GH and a control group of 102 normotensive pregnant (NP) women. A robust multifactor dimensionality reduction analysis was used to characterize gene-gene interactions. Although no significant genotype combinations were observed for the comparison between the GH and NP groups (P>0.05), the combination of MMP-9-1562CC with VEGF-634GG was more frequent in NP women than in women with PE (P