Mutational Screening for Mitochondrial tRNA Genes in 100 Women with Pre-Eclampsia

Abstract

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.