Genetic variants in microRNA machinery genes are associated [corrected] with idiopathic recurrent pregnancy loss risk.
Genetic variants in microRNA machinery genes are associated [corrected] with idiopathic recurrent pregnancy loss risk.
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DOI：
10.1371/journal.pone.0095803
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kim NK
中科院分区：
文献类型：
--
作者：
Jung YW;Jeon YJ;Rah H;Kim JH;Shin JE;Choi DH;Cha SH;Kim NK
在滋养细胞中发现了参与microRNA （miRNA）生物发生的关键分子，如DROSHA、XPO5和DICER，证实了miRNA生物发生途径在人胎盘中是活跃的。此外，miRNAs还调节着床期炎症反应相关的子宫基因表达，参与母胎免疫耐受。本研究的目的是证明miRNA机制基因的遗传多态性是否与韩国女性特发性复发性妊娠丢失（RPL）有关。我们对238名对照组和338名在1999年至2010年间至少连续两次流产的妇女进行了病例对照研究。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法分析DICER rs3742330、DROSHA rs10719、RAN GTPase (RAN) rs14035、exportin-5 (XPO5) rs11077等miRNA机械基因的基因型。在多因素分析中，经产妇年龄调整后，RPL的logistic优势比（ORs）估计为95%置信区间（CI）。采用多因子降维（MDR）方法对四种基因多态性位点间的相互作用进行了评价。RAN rs14035 CC基因型和DICER rs3742330/DROSHA rs10719 GG/TC+CC、rs3742330/RAN rs14035 GG/CC、DICER rs3742330/RAN rs14035 GG/CC、DICER rs3742330/RAN rs11077 GG/AC+CC组合与RPL风险增加显著相关，而RAN rs14035 CT、DICER rs3742330/RAN rs14035 AA+AG/CT+TT、DROSHA rs10719/RAN rs14035 TC+CC/CT+TT和RAN rs14035/XPO5 rs11077 CT+TT/AA组合可降低RPL风险。RPL组出现A-T-T-C和G-C-T-A等位基因组合（DICER/DROSHA/RAN/XPO5）的频率是对照组的20倍。我们的研究证实了RPL的发生与miRNA机制基因RAN多态性和DROSHA/DICER联合基因型之间的关系。
Key molecules involved in microRNA (miRNA) biogenesis, such as DROSHA, XPO5, and DICER, have been identified in trophoblast cells, confirming that the miRNA biogenesis pathway is active in human placenta. In addition, miRNAs regulate uterine gene expression associated with inflammatory responses during the peri-implantation period and participate in maternal-fetal immune tolerance. The purpose of this study was to demonstrate whether genetic polymorphisms in miRNA machinery genes show an association with idiopathic recurrent pregnancy loss (RPL) in Korean women. We performed a case-control study with 238 controls and 338 women who had experienced at least two consecutive pregnancy losses between 1999 and 2010. Genotypes of miRNA machinery genes, including DICER rs3742330, DROSHA rs10719, RAN GTPase (RAN) rs14035, and exportin-5 (XPO5) rs11077 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The logistic odds ratios (ORs) of RPL were estimated with a 95% confidence interval (CI) in multivariate analysis after maternal age adjustment. Gene-gene interactions among the loci of the four gene polymorphisms were evaluated using the multifactor dimensionality reduction (MDR) method. The RAN rs14035 CC genotype and DICER rs3742330/DROSHA rs10719 GG/TC+CC, rs3742330/RAN rs14035 GG/CC, and DICER rs3742330/XPO5 rs11077 GG/AC+CC combinations were significantly associated with increased RPL risk, whereas the RAN rs14035 CT, DICER rs3742330/RAN rs14035 AA+AG/CT+TT, DROSHA rs10719/RAN rs14035 TC+CC/CT+TT, and RAN rs14035/XPO5 rs11077 CT+TT/AA combinations reduced RPL risk. The A-T-T-C and G-C-T-A allele combinations (DICER/DROSHA/RAN/XPO5) were 20 times more frequent in the RPL group than in the control group. Our study demonstrates the relationship between RPL development and the polymorphism of the miRNA machinery gene RAN and combined genotype of DROSHA/DICER.
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DOI：
10.1038/nrm2718
发表时间：
2009-07
期刊：
Nature reviews. Molecular cell biology
影响因子：
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作者：
通讯作者：
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影响因子：
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作者：
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10.1073/pnas.0705917104
发表时间：
2007-09-18
影响因子：
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作者：
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通讯作者：
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