Rheumatology and Immunology Department, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Cardiovascular Medicine Department, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Front Immunol. 2024 Oct 9;15:1409969. doi: 10.3389/fimmu.2024.1409969. eCollection 2024.
Mitochondrial DNA (mtDNA) plays an important role in autoimmune diseases (AD), yet the relationship between mitochondria and autoimmune disease is controversial. This study employed bidirectional Mendelian randomization (MR) to explore the causal relationship between mtDNA copy number and 13 ADs (including ankylosing spondylitis [AS], Crohn's disease [CD], juvenile rheumatoid arthritis [JRA], polymyalgia rheumatica [PMR], psoriasis [PSO], rheumatoid arthritis [RA], Sjogren's syndrome [SS], systemic lupus erythematosus [SLE], thyrotoxicosis, type 1 diabetes mellitus [T1DM], ulcerative colitis [UC], and vitiligo).
A two-sample MR analysis was performed to assess the causal relationship between mtDNA copy number and AD. Genome-wide association study (GWAS) for mtDNA copy number were obtained from the UK Biobank (UKBB), while those associated with AD were sourced from the FinnGen Biobank. Inverse variance weighting (IVW) was the primary analysis method, complemented by three sensitivity analyses (MR-Egger, weighted median, weighted mode) to validate the results.
IVW MR analysis identified significant associations between mtDNA copy number and CD (OR=2.51, 95% CI 1.56-4.22, P<0.001), JRA (OR=1.87, 95% CI 1.17-7.65, P=0.022), RA (OR=1.71, 95%CI 1.18-2.47, P=0.004), thyrotoxicosis (OR=0.51, 95% CI0.27-0.96, P=0.038), and T1DM (OR=0.51, 95% CI 0.27-0.96, P=0.038). Sensitivity analyses indicated no horizontal pleiotropy.
Our study revealed a potential causal relationship between mtDNA copy number and ADs, indicating that these markers may be relevant in exploring new therapeutic approaches.
线粒体 DNA（mtDNA）在自身免疫性疾病（AD）中发挥着重要作用，但线粒体与自身免疫性疾病之间的关系仍存在争议。本研究采用双向孟德尔随机化（MR）方法，探讨 mtDNA 拷贝数与 13 种 AD（包括强直性脊柱炎[AS]、克罗恩病[CD]、幼年特发性关节炎[JRA]、多发性肌痛[PMR]、银屑病[PSO]、类风湿关节炎[RA]、干燥综合征[SS]、系统性红斑狼疮[SLE]、甲状腺毒症、1 型糖尿病[T1DM]、溃疡性结肠炎[UC]和白癜风）之间的因果关系。
采用两样本 MR 分析评估 mtDNA 拷贝数与 AD 之间的因果关系。mtDNA 拷贝数的全基因组关联研究（GWAS）来自英国生物银行（UKBB），而与 AD 相关的研究则来自芬兰基因生物银行（FinnGen Biobank）。主要分析方法为逆方差加权（IVW），并采用三种敏感性分析（MR-Egger、加权中位数、加权众数）验证结果。
IVW MR 分析发现 mtDNA 拷贝数与 CD（OR=2.51，95%CI 1.56-4.22，P<0.001）、JRA（OR=1.87，95%CI 1.17-7.65，P=0.022）、RA（OR=1.71，95%CI 1.18-2.47，P=0.004）、甲状腺毒症（OR=0.51，95%CI 0.27-0.96，P=0.038）和 T1DM（OR=0.51，95%CI 0.27-0.96，P=0.038）之间存在显著关联。敏感性分析表明不存在水平性偏倚。
本研究揭示了 mtDNA 拷贝数与 AD 之间的潜在因果关系，提示这些标志物可能与探索新的治疗方法有关。
