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早发型子痫前期与亚甲基四氢叶酸还原酶(MTHFR)及凝血因子V Leiden(FVL)基因多态性有关。

The early-onset preeclampsia is associated with MTHFR and FVL polymorphisms.

作者信息

Salimi Saeedeh, Saravani Mohsen, Yaghmaei Minoo, Fazlali Zeinab, Mokhtari Mojgan, Naghavi Anoosh, Farajian-Mashhadi Farzaneh

机构信息

Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.

出版信息

Arch Gynecol Obstet. 2015 Jun;291(6):1303-12. doi: 10.1007/s00404-014-3561-5. Epub 2014 Dec 6.

Abstract

PURPOSE

The aim of this study was to examine the association of factor V Leiden, prothrombin and methylenetetrahydrofolate reductase (MTHFR) polymorphisms and preeclampsia (PE) in Southeast of Iran.

METHODS

This case-control study was performed on 192 preeclamptic and 196 normotensive pregnant women. Single nucleotide polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Tetra ARMS methods.

RESULTS

No significant differences were observed in distribution of MTHFR C677T and FVL polymorphisms between two groups. There was a significant difference in frequency of 1298AC genotype in PE pregnant women compared to controls (P = 0.03). No 20210A allele of prothrombin gene was observed in this population. The analysis of MTHFR and factor V Leiden polymorphisms between early-onset PE (EOPE) and late-onset PE (LOPE) showed significant differences in MTHFR A1298C polymorphism (AC and CC vs AA, P = 0.012 and P = 0.006, respectively) and G1691A polymorphism of FVL(GA vs GG, P = 0.03). Moreover, the analysis of three SNPs between EOPE and controls showed significant differences in MTHFR C677T (CT + TT vs CC, P = 0.035) and MTHFR A1298C (AC and CC vs AA, P = 0.001 and P = 0.006, respectively) polymorphisms. The synergic effect of MTHFR A1298C and C677T polymorphisms showed increased risk of EOPE.

CONCLUSION

MTHFR A1298C polymorphism was associated with PE. Although MTHFR C677T and FVL polymorphisms did not differ between PE patients and controls, significant differences in MTHFR A1298C, C677T and FVL polymorphisms between EOPE and LOPE/controls were observed. The synergic effect of MTHFR variants could increase PE and EOPE risk.

摘要

目的

本研究旨在探讨伊朗东南部地区凝血因子V莱顿突变、凝血酶原及亚甲基四氢叶酸还原酶(MTHFR)基因多态性与子痫前期(PE)之间的关联。

方法

本病例对照研究纳入了192例子痫前期孕妇和196例血压正常的孕妇。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)和四引物扩增受阻突变系统(Tetra ARMS)方法对单核苷酸多态性进行基因分型。

结果

两组间MTHFR C677T和凝血因子V莱顿突变(FVL)多态性分布无显著差异。与对照组相比,子痫前期孕妇中1298AC基因型频率存在显著差异(P = 0.03)。该人群中未观察到凝血酶原基因的20210A等位基因。早发型子痫前期(EOPE)和晚发型子痫前期(LOPE)之间MTHFR和凝血因子V莱顿突变多态性分析显示,MTHFR A1298C多态性存在显著差异(AC和CC与AA相比,P分别为0.012和0.006)以及FVL的G1691A多态性存在显著差异(GA与GG相比,P = 0.03)。此外,EOPE与对照组之间三个单核苷酸多态性(SNP)分析显示,MTHFR C677T(CT + TT与CC相比,P = 0.035)和MTHFR A1298C(AC和CC与AA相比,P分别为0.001和0.006)多态性存在显著差异。MTHFR A1298C和C677T多态性的协同作用显示EOPE风险增加。

结论

MTHFR A1298C多态性与子痫前期相关。尽管子痫前期患者与对照组之间MTHFR C677T和FVL多态性无差异,但EOPE与LOPE/对照组之间MTHFR A1298C、C677T和FVL多态性存在显著差异。MTHFR变异的协同作用可能增加子痫前期和早发型子痫前期的风险。

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