Jang Haerin, Kim Mina, Hong Jung Yeon, Cho Hyung Ju, Kim Chang Hoon, Kim Yoon Hee, Sohn Myung Hyun, Kim Kyung Won
Department of Pediatrics, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Institute of Allergy, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Allergy Asthma Immunol Res. 2020 Sep;12(5):877-884. doi: 10.4168/aair.2020.12.5.877.
The mitochondrial genome encodes core catalytic peptides that affect major metabolic processes within a cell. Here, we investigated the association between mitochondrial DNA (mtDNA) variants and allergic diseases, including atopic dermatitis (AD) and asthma, alongside heteroplasmy within the mtDNA in subjects with allergic sensitization. We collected genotype data from 973 subjects with allergic sensitization, consisting of 632 children with AD, 498 children with asthma, and 481 healthy controls by extracting DNA from their blood samples. Fisher's exact test was used to investigate mtDNA and nuclear DNA variants related to mitochondrial function (MT-nDNA) to identify their association with allergic diseases. Among the 69 mtDNA variants, rs28357671 located on the gene displayed statistically significant associations with allergic diseases (Bonferroni-corrected < 7.25E-4), while 6, 4, and 2 genes were associated with allergic sensitization, AD, and asthma, respectively ( < 0.0002), including , , and among the MT-nDNA genes. Heteroplasmy of mitochondrial DNA associated with allergic sensitization was evaluated in a separate cohort of patients consisting of 59 subjects with allergic sensitization and 52 controls. Heteroplasmy was verified when a patient carried both alleles of a mitochondrial single-nucleotide polymorphism (SNP) when clustered. One of the 134 mitochondrial SNPs showed heteroplasmy at a level of 0.4313 when clustering was applied. The probe sequence located at mitochondrial position 16217 and within the D-loop, which acts as a major control site for mtDNA expression. This is the first study to evaluate the association between mitochondrial DNA variants and allergic diseases. A harmonized effect of genes related to mitochondrial function may contribute to the risk of allergic diseases.
线粒体基因组编码影响细胞内主要代谢过程的核心催化肽。在此，我们研究了线粒体DNA（mtDNA）变异与过敏性疾病（包括特应性皮炎（AD）和哮喘）之间的关联，以及过敏致敏受试者mtDNA中的异质性。我们通过从973名过敏致敏受试者的血液样本中提取DNA，收集了基因型数据，其中包括632名AD儿童、498名哮喘儿童和481名健康对照。使用Fisher精确检验来研究与线粒体功能相关的mtDNA和核DNA变异（MT-nDNA），以确定它们与过敏性疾病的关联。在69个mtDNA变异中，位于基因上的rs28357671与过敏性疾病显示出统计学上的显著关联（Bonferroni校正P<7.25E-4），而分别有6个、4个和2个基因与过敏致敏、AD和哮喘相关（P<0.0002），包括MT-nDNA基因中的、和。在由59名过敏致敏患者和52名对照组成的另一组患者中评估了与过敏致敏相关的线粒体DNA异质性。当患者聚类时携带线粒体单核苷酸多态性（SNP）的两个等位基因时，异质性得到验证。在应用聚类时，134个线粒体SNP中的一个显示异质性水平为0.4313。探针序列位于线粒体位置16217且在D环内，D环是mtDNA表达的主要控制位点。这是第一项评估线粒体DNA变异与过敏性疾病之间关联的研究。与线粒体功能相关的基因的协同作用可能会增加患过敏性疾病的风险。
