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

异质性 线粒体DNA 生物 遗传学 NADH脱氢酶 基因 非同义代换 单倍型 基因型 基因组
作者
Huajie Yuan,Lingling Wang,Song Wang,Linge Li,Qingping Liu,Yan Wang,Yuping Yang,Hua Zhang
出处
期刊:Allergy, Asthma & Clinical Immunology [BioMed Central]
卷期号:20 (1)
标识
DOI:10.1186/s13223-024-00881-z
摘要

Abstract Background 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. Methods 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. Results 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). Conclusions In a two-stage analysis of associations between AR and mtDNA variations, mitochondrial gene ma p s of Chinese patients with AR indicated that the ATP6 gene was probably associated with AR at the single-variant level.
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