# Two-stage association study of mitochondrial DNA variants in allergic rhinitis

## TL;DR

This study investigates the link between mitochondrial DNA variations and allergic rhinitis in Chinese individuals, finding a potential association with the ATP6 gene.

## Contribution

The study is the first to explore mitochondrial DNA variants in allergic rhinitis using a two-stage association approach in a Chinese population.

## Key findings

- No significant differences in mitochondrial heteroplasmy or gene-level associations were found after Bonferroni correction.
- The nonsynonymous variant rs3135028 in ATP6 was associated with reduced AR risk in both discovery and validation cohorts.
- Lower mRNA levels of MT-ATP6 were observed in nasal mucosal tissue of AR individuals compared to controls.

## Abstract

Correlations between mitochondrial DNA (mtDNA) and allergic rhinitis (AR) have not been reported before. This study aimed to better understand the mitochondrial genome profile with AR and to investigate the associations between AR in China and the mitochondrial genome at a single variant and gene level.

Mitochondrial sequencing was conducted on a total of 134 unrelated individual subjects (68 patients with AR, 66 healthy controls) at discovery stage. Heteroplasmy was analyzed using the Mann-Whitney U test. Sequence kernel association tests (SKAT) were conducted to study the association between mitochondrial genes and AR. Single-variant analysis was performed using logistic regression analysis and further validated in 120 subjects (69 patients with AR, 51 healthy controls). Candidate genes were further explored based on differences in mRNA and protein abundance in nasal mucosal tissue.

In the discovery stage, 886 variants, including 836 SNV and 50 indels, were identified with mitochondrial sequencing. No statistically significant differences were identified for the mitochondrial heteroplasmy or SKAT analysis between these two groups after applying a Boferroni correction. One nonsynonymous variants, rs3135028 (MT8584.G/A) in ATP6, was related to a reduced risk of AR in both the discovery and validation cohorts. Furthermore, mRNA levels of MT-ATP6 in nasal mucosal tissue were significantly lower in AR individuals than in controls (P < 0.05).

In a two-stage analysis of associations between AR and mtDNA variations, mitochondrial gene maps of Chinese patients with AR indicated that the ATP6 gene was probably associated with AR at the single-variant level.

The online version contains supplementary material available at 10.1186/s13223-024-00881-z.