RESUMEN
This study aimed to explore the role of mitochondrial DNA copy number (mtDNAcn) in the risk, glucocorticoid (GC) effectiveness, and prognosis of systemic lupus erythematosus (SLE) and its interactions with environmental factors and tumor necrosis factor receptor-associated protein 1 (TRAP1) genetic polymorphisms. We first conducted a case-control study of 1198 subjects (595 SLE patients and 603 healthy controls). Subsequently, we followed up with patients to assess the effectiveness of GC treatment and the prognosis of SLE. Real-time fluorescent quantitative PCR (qPCR) was used to quantify mtDNAcn. Associations were estimated using logistic regression, and prognosis analysis was performed using Kaplan-Meier analysis and Cox proportional hazards models. Interactions on multiplicative and additive scales were also evaluated. Individuals with low mtDNAcn had an increased risk of SLE (P < 0.001). Low mtDNAcn was associated with poor GC effectiveness in patients with spicy food consumption or with arthritis (P < 0.05). mtDNAcn was significantly related to the prognosis of SLE in the drinking subgroup (P = 0.018). Furthermore, we found significant interactions between mtDNAcn and environmental factors/TRAP1 genetic polymorphisms on the risk, GC effectiveness, and prognosis of SLE. Our data suggest that low mtDNAcn is associated with an increased risk of SLE. Alteration of mtDNAcn may be associated with GC effectiveness and prognosis in certain subgroups of SLE. The interactions between mtDNAcn, environmental factors, and TRAP1 gene polymorphisms may jointly affect the risk, GC effectiveness, and prognosis of SLE.