Introduction: 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 tRNA (mt-tRNA) variants and PE. Methods: The mt-tRNA variants in a cohort of 100 pregnant women with PE and 100 healthy subjects were examined by PCR-Sanger sequencing. Moreover, the phylogenetic conservation analysis, mitochondrial haplogroup analysis, and pathogenicity scoring system were used to assess the potential pathogenicity of these tRNA variants. Results: We identified five possible pathogenic mt-tRNA variants: tRNA^Phe A608G, tRNA^Ile A4263G, tRNA^Ala T5587C, tRNA^Leu(CUN) G12294C, and tRNA^Pro G15995A. We noticed that these variants were not detected in control subjects and occurred at the positions which were extremely conserved. Alternations in tRNA structure caused by these variants may lead to the failures in tRNA metabolism, which may subsequently 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. Conclusion: 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.
Hum Hered 2022;87:87–95

中文翻译：

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100 名先兆子痫妇女线粒体 tRNA 基因突变筛查

简介：已发现由致病性线粒体 DNA (mtDNA) 突变引起的线粒体功能受损与先兆子痫 (PE) 相关。然而，PE 的潜在机制仍未确定。本研究的目的是评估线粒体 tRNA (mt-tRNA) 变体与 PE 之间的关系。方法：通过 PCR-Sanger 测序检测 100 名患有 PE 的孕妇和 100 名健康受试者的 mt-tRNA 变异。此外，系统发育保守分析、线粒体单倍群分析和致病性评分系统被用于评估这些 tRNA 变异的潜在致病性。结果：我们确定了五种可能的致病性 mt-tRNA 变异：tRNA ^Phe A608G、tRNA^Ile A4263G、tRNA ^Ala T5587C、tRNA ^Leu(CUN) G12294C 和 tRNA ^Pro G15995A。我们注意到这些变异在对照受试者中未检测到，并且发生在极其保守的位置。由这些变异引起的 tRNA 结构改变可能导致 tRNA 代谢失败，随后可能导致线粒体翻译和呼吸链功能受损。因此，mt-tRNA 变体可能参与 PE 的发病机制。结论：综上所述，我们的数据表明 mt-tRNA 基因变异是 PE 的重要贡献者；建议筛查 mt-tRNA 变体以早期检测和预防 PE。
嗡嗡声 2022 年；87:87–95