Mutational Analysis of Mitochondrial tRNA Genes in Patients with Asthma

Mitochondria are autonomous cellular organelles that oversee a variety of functions such as metabolism, energy production, calcium buffering, and cell fate determination. Most recently, mitochondrial dysfunction caused by mitochondrial mutations played important roles in the pathogenesis of asthma. However, the frequency of mitochondrial tRNA mutations in asthma is largely unknown.

Overall, 200 patients with asthma and 100 healthy control subjects were recruited between Jan 2015 and Dec 2015 at the Guangming New District People's Hospital, Shenzhen, Guangdong Province, China. We first performed PCR amplification of the mitochondrial tRNA genes and subsequently sequenced the PCR products, and we used the pathogenicity scoring system to evaluate the potential role of these mutations.

Two patients carrying the tRNA^Thr G15927A mutation, three patients carrying the tRNA^Ala T5655C mutation and one patient carrying the tRNA^Glu A14693G mutation, these mutations were absent in healthy controls. Moreover, these mutations located at positions highly conserved between different species, and may cause a failure in mitochondrial tRNA metabolism, consequently result in mitochondrial dysfunction that responsible for asthma. In addition, the pathogenicity scoring system showed that these mutations should be regarded as "pathogenic".

Mitochondrial tRNA mutations caused the mitochondrial dysfunction may be involved in the pathogenesis of asthma. Thus, this study provided novel insight into the molecular mechanism underlying mitochondrial tRNA mutations in asthma. Moreover, screening for the mitochondrial tRNA mutations was advised for the diagnosis of patients with asthma.