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IL-27 变异可能是子痫前期的遗传风险因素:基于遗传多态性、单倍型和计算机模拟方法。

IL-27 variants might be genetic risk factors for preeclampsia: based on genetic polymorphisms, haplotypes and in silico approach.

机构信息

Department of Biology, Faculty of Science, University of Sistan and Baluchestan, Zahedan, Iran.

Department of Cell and Molecular Biology, Kosar University of Bojnord, Bojnord, Iran.

出版信息

Mol Biol Rep. 2020 Oct;47(10):7929-7940. doi: 10.1007/s11033-020-05871-z. Epub 2020 Oct 3.

Abstract

Pre-eclampsia (PE) is a disorder that occurs only during pregnancy. PE is associated with neonate mortality and morbidity. Overexpression of IL-27 and its receptor have been reported frequently in the trophoblast cells of patients with PE. In this study, we aimed to evaluate the relationship between genetic polymorphisms of IL-27 rs153109, and rs17855750 in an Iranian cohort of 170 PE patients and 170 normal pregnant women using the PCR-RFLP method. In the total PE, the frequency of heterozygous and mutant homozygous genotypes of rs153109 was significantly higher, severe, and mild PE groups. The genotypes and alleles frequencies of rs17855750 gene polymorphism were associated with PE susceptibility in total, severe and early-onset sub-group patients. Haplotype analysis of IL-27 rs153109 and rs17855750 polymorphisms revealed that the mutant GG haplotype frequencies significantly increased the risk of preeclampsia in total PE and different sub-group patients, while the wild AT haplotypes were associated with decreased risk of pre-eclampsia in total and sub-group patients. The in-silico analysis showed the transition of allele A to allele G in rs153109 SNP, would lead to create a new binding site and consequently may lead to changes in IL-27 gene expression. We found that rs17855750 A>G polymorphism might be influence the function of IL-27 protein. The data attained in our study propose the incidence of IL-27rs153109 and rs17855750 SNPs might be capable to be utilized as indicators for the genetic susceptibility to PE.

摘要

子痫前期 (PE) 是一种仅在妊娠期间发生的疾病。PE 与新生儿死亡率和发病率有关。已有研究报道,PE 患者的滋养细胞中 IL-27 及其受体的表达常常过度。在这项研究中,我们旨在使用 PCR-RFLP 方法评估 IL-27 rs153109 和 rs17855750 基因多态性与 170 例伊朗 PE 患者和 170 例正常孕妇之间的关系。在总 PE 患者中,杂合子和突变纯合子基因型 rs153109 的频率在重度和轻度 PE 组中显著升高。rs17855750 基因多态性的基因型和等位基因频率与总、重度和早发型亚组患者的 PE 易感性相关。IL-27 rs153109 和 rs17855750 多态性的单体型分析表明,突变 GG 单体型频率显著增加了总 PE 和不同亚组患者发生子痫前期的风险,而野生 AT 单体型与总 PE 和亚组患者子痫前期风险降低相关。基于计算机的分析表明,rs153109 SNP 中的等位基因 A 向等位基因 G 的转变,会导致产生一个新的结合位点,从而可能导致 IL-27 基因表达的变化。我们发现 rs17855750 A>G 多态性可能会影响 IL-27 蛋白的功能。我们的研究数据表明,IL-27rs153109 和 rs17855750 SNP 的发生率可能能够作为 PE 遗传易感性的指标。

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