White blood cell mitochondrial DNA copy number is decreased in rheumatoid arthritis and linked with risk factors. A twin study.

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.