Association study of mitochondrial genetic polymorphisms in asthmatic children

Abstract

It has been suggested that mitochondrial dysfunction plays a role in the pathogenesis of asthma. To test whether mitochondrial variants influence the risk of asthma, we analyzed 16,158 mtSNPs in a sample of 372 asthmatic children and 395 healthy children using the DNA pooling technique and genome wide association analysis. Stratified analysis by sex was performed to explain the differences observed between sexes in the etiology of asthma. Different variants were detected to be significant in the sample of girls and boys with the smallest adjusted p values being 1.4 × 10(-09) (mt5295) and 3.6 × 10(-12) (mt16158), respectively. Most of the significant locations found in boys are within the CYB gene and the non-coding region. For girls, most of the significant mtSNPs lie within NADH-dehydrogenase-subunits. The variants reported here have not previously been described in connection with asthma. Although further studies in other cohorts are needed to confirm these findings our study highlights the importance of the mitochondria among the factors that contribute to the risk of asthma.

Keywords: 16S RNA; Asthma; Cyt b; Genome wide association; HVR1; Hypervariability Region 1; IgE; Immunoglobulin E; Mitochondrial genome; NADH; NADH dehydrogenase subunit 2; ND2; OXPHOS; Pool data; QC; ROS; Ribosomal Ribonucleic Acid; SNP; basepairs; bp; cytochrome b; mitochondrial single nucleotide polymorphism; mitochondrially encoded 16S RNA; mtSNP; nicotinamide adenine dinucleotide; oxidative phosphorylation; quality control; rRNA; reactive oxygen species; single nucleotide polymorphism.