Two-stage association study of mitochondrial DNA variants in allergic rhinitis
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-02-01
|
| Series: | Allergy, Asthma & Clinical Immunology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13223-024-00881-z |
| _version_ | 1797274212781522944 |
|---|---|
| author | Huajie Yuan Lingling Wang Song Wang Linge Li Qingping Liu Yan Wang Yuping Yang Hua Zhang |
| author_facet | Huajie Yuan Lingling Wang Song Wang Linge Li Qingping Liu Yan Wang Yuping Yang Hua Zhang |
| author_sort | Huajie Yuan |
| collection | DOAJ |
| description | 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 maps of Chinese patients with AR indicated that the ATP6 gene was probably associated with AR at the single-variant level. |
| first_indexed | 2024-03-07T14:56:04Z |
| format | Article |
| id | doaj.art-13c74fcdb1dd4c7286c468028d4dade6 |
| institution | Directory Open Access Journal |
| issn | 1710-1492 |
| language | English |
| last_indexed | 2024-03-07T14:56:04Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Allergy, Asthma & Clinical Immunology |
| spelling | doaj.art-13c74fcdb1dd4c7286c468028d4dade62024-03-05T19:25:14ZengBMCAllergy, Asthma & Clinical Immunology1710-14922024-02-0120111010.1186/s13223-024-00881-zTwo-stage association study of mitochondrial DNA variants in allergic rhinitisHuajie Yuan0Lingling Wang1Song Wang2Linge Li3Qingping Liu4Yan Wang5Yuping Yang6Hua Zhang7Department of Otolaryngology, Xinjiang Medical University Affiliated First HospitalDepartment of Otolaryngology, Xinjiang Medical University Affiliated First HospitalDepartment of Otolaryngology, Xinjiang Medical University Affiliated First HospitalDepartment of Otolaryngology, Xinjiang Medical University Affiliated First HospitalDepartment of Otolaryngology, Xinjiang Medical University Affiliated First HospitalDepartment of Otolaryngology, Xinjiang Medical University Affiliated First HospitalDepartment of Otolaryngology, Xinjiang Medical University Affiliated First HospitalDepartment of Otolaryngology, Xinjiang Medical University Affiliated First HospitalAbstract 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 maps of Chinese patients with AR indicated that the ATP6 gene was probably associated with AR at the single-variant level.https://doi.org/10.1186/s13223-024-00881-zAllergic rhinitisMitochondrialGeneVariants |
| spellingShingle | Huajie Yuan Lingling Wang Song Wang Linge Li Qingping Liu Yan Wang Yuping Yang Hua Zhang Two-stage association study of mitochondrial DNA variants in allergic rhinitis Allergy, Asthma & Clinical Immunology Allergic rhinitis Mitochondrial Gene Variants |
| title | Two-stage association study of mitochondrial DNA variants in allergic rhinitis |
| title_full | Two-stage association study of mitochondrial DNA variants in allergic rhinitis |
| title_fullStr | Two-stage association study of mitochondrial DNA variants in allergic rhinitis |
| title_full_unstemmed | Two-stage association study of mitochondrial DNA variants in allergic rhinitis |
| title_short | Two-stage association study of mitochondrial DNA variants in allergic rhinitis |
| title_sort | two stage association study of mitochondrial dna variants in allergic rhinitis |
| topic | Allergic rhinitis Mitochondrial Gene Variants |
| url | https://doi.org/10.1186/s13223-024-00881-z |
| work_keys_str_mv | AT huajieyuan twostageassociationstudyofmitochondrialdnavariantsinallergicrhinitis AT linglingwang twostageassociationstudyofmitochondrialdnavariantsinallergicrhinitis AT songwang twostageassociationstudyofmitochondrialdnavariantsinallergicrhinitis AT lingeli twostageassociationstudyofmitochondrialdnavariantsinallergicrhinitis AT qingpingliu twostageassociationstudyofmitochondrialdnavariantsinallergicrhinitis AT yanwang twostageassociationstudyofmitochondrialdnavariantsinallergicrhinitis AT yupingyang twostageassociationstudyofmitochondrialdnavariantsinallergicrhinitis AT huazhang twostageassociationstudyofmitochondrialdnavariantsinallergicrhinitis |