Department of Internal Medicine, Odense University Hospital, Svendborg, Denmark; Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark.
Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark; Unit of Human Genetics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
J Autoimmun. 2019 Jan;96:142-146. doi: 10.1016/j.jaut.2018.09.008. Epub 2018 Oct 14.
Low mitochondrial DNA copy number (mtDNA CN) has been associated with e.g. cancer, cardiovascular and autoimmune diseases. We aimed to study a potential association between mtDNA CN and rheumatoid arthritis (RA). The relative quantity of mitochondrial DNA compared to nuclear DNA was measured in peripheral white blood cells from 149 RA affected twin pairs and 1321 non-affected twin pairs. Multiple regression analysis including RA discordant twin pairs was performed in order to separate specific effects of RA and familial RA predisposition using non-RA affected twin pairs as reference group. In addition, we performed a twin pair level analysis including only RA discordant twin pairs evaluating the effect of cell type, auto antibodies and RA genetic risk factors. Both the RA twins and their non-affected co-twins had significantly lower mtDNA CN than non-affected twins (-28.7 and -23.1 mtDNA CN, respectively). Adjusting for cell count attenuated these differences (-23.1 mtDNA CN and -20.1 mtDNA CN respectively). Within RA discordant twin pairs PTPN22(T) positive RA twins had a significantly lower amount than their co-twins (-16.3 mtDNA CN). PTPN22(T) had no effect among twins from non-affected twin pairs. MtDNA CN is significantly lower in persons with established RA and in predisposed non-affected RA co-twins suggesting that mitochondrial variation may be involved in the RA disease pathways. Our results also suggest that the RA associated genetic risk factor, PTPN22(T), further decreases the mtDNA CN, but only in carriers with established RA.
线粒体 DNA 拷贝数 (mtDNA CN) 较低与癌症、心血管和自身免疫性疾病等有关。我们旨在研究 mtDNA CN 与类风湿关节炎 (RA) 之间的潜在关联。在 149 对 RA 患病双胞胎和 1321 对非患病双胞胎的外周白细胞中测量了线粒体 DNA 与核 DNA 的相对数量。为了使用非 RA 患病双胞胎作为参考组，分离 RA 和家族性 RA 易感性的特定影响，对 RA 不一致的双胞胎进行了包括多重回归分析。此外，我们仅对 RA 不一致的双胞胎进行了双胞胎水平分析，评估了细胞类型、自身抗体和 RA 遗传风险因素的影响。RA 双胞胎及其未患病的同卵双胞胎的 mtDNA CN 明显低于未患病的双胞胎 (-28.7 和 -23.1 mtDNA CN)。调整细胞计数后，这些差异减弱 (-23.1 mtDNA CN 和 -20.1 mtDNA CN)。在 RA 不一致的双胞胎中，PTPN22(T) 阳性 RA 双胞胎的 mtDNA CN 明显低于其同卵双胞胎 (-16.3 mtDNA CN)。在非患病双胞胎中，PTPN22(T) 对双胞胎没有影响。已确诊 RA 患者和易患未患病 RA 的同卵双胞胎的 mtDNA CN 明显较低，表明线粒体变异可能参与了 RA 疾病途径。我们的结果还表明，RA 相关的遗传风险因素 PTPN22(T) 进一步降低了 mtDNA CN，但仅在已确诊的 RA 携带者中。
