Zhou Baohua, Chu Xuelian, Zhang Caijuan, Liang Xiufeng
Hum Hered. 2022 Jul 18. doi: 10.1159/000525663.
Impairment of mitochondrial function caused by pathogenic mitochondrial DNA (mtDNA) mutations has been found to be associated with pre-eclampsia (PE). However, the underlying mechanism of PE remains poorly undetermined. The aim of this study is to evaluate the relationship between mitochondrial tRNAs (mt-tRNAs) variants and PE.
The mt-tRNAs variants in a cohort of 100 pregnant women with PE and 100 healthy subjects were examined by PCR-Sager sequencing. Moreover, the phylogenetic conservation analysis, mitochondrial haplogroup analysis, as well as pathogenicity scoring system were used to assess the potential pathogenicity of these tRNA variants.
We identified five possible pathogenic mt-tRNA variants: tRNAPhe A608G, tRNAIle A4263G, tRNAAla T5587C, tRNALeu(CUN) G12294C and tRNAPro G15995A. We noticed that these variants were not detected in control subjects and occurred at the positions which were extremely conserved. Alternations in tRNAs structure caused by these variants may lead to the failures in tRNAs metabolism, which may subsequently may lead to the impairment of mitochondrial translation, as well as the respiratory chain functions. Thus, mt-tRNA variants may be involved in the pathogenesis of PE.
Taken together, our data indicated that variants in mt-tRNA genes were the important contributors to PE; screening for mt-tRNA variants was recommended for early detection and prevention of PE.
已发现由致病性线粒体DNA（mtDNA）突变引起的线粒体功能损害与子痫前期（PE）有关。然而，PE的潜在机制仍不清楚。本研究的目的是评估线粒体tRNA（mt-tRNA）变体与PE之间的关系。
采用PCR-Sanger测序法检测100例PE孕妇和100例健康受试者队列中的mt-tRNA变体。此外，利用系统发育保守性分析、线粒体单倍群分析以及致病性评分系统来评估这些tRNA变体的潜在致病性。
我们鉴定出五种可能的致病性mt-tRNA变体：tRNAPhe A608G、tRNAIle A4263G、tRNAAla T5587C、tRNALeu（CUN）G12294C和tRNAPro G15995A。我们注意到这些变体在对照受试者中未被检测到，且发生在极度保守的位置。这些变体引起的tRNA结构改变可能导致tRNA代谢失败，进而可能导致线粒体翻译以及呼吸链功能受损。因此，mt-tRNA变体可能参与了PE的发病机制。
综上所述，我们的数据表明mt-tRNA基因变体是PE的重要促成因素；建议筛查mt-tRNA变体以早期发现和预防PE。
