Association of Mitochondrial DNA Genetic Variants With Depression and Anxiety in Chinese Patients With Systemic Lupus Erythematosus.

OBJECTIVE

To explore the association of mitochondrial DNA (mtDNA) genetic variants, including single nucleotide variants (SNVs), insertions and deletions (InDels), and copy number variations (CNVs), with depression and anxiety in Chinese patients with systemic lupus erythematosus (SLE).

METHODS

A two-stage study of 530 patients with SLE was conducted to explore the association between mtDNA genetic variants (SNVs and InDels) and depression and anxiety. A total of 499 patients with SLE were recruited to explore the association between mtDNA CNVs and depression and anxiety. Meanwhile, the patients were followed up for 12 weeks to observe the improvement of depression and anxiety. The levels of reactive oxygen species (ROS), adenosine triphosphate (ATP), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were detected.

RESULTS

Two mtDNA SNVs (C16291T, A16399G) in the displacement loop (D-loop) region were associated with depression in patients with SLE (PBH = 0.003, PBH = 0.007). Two mtDNA SNVs (T9950C, T16140C) in the cytochrome c oxidase subunit III (COX3) gene and D-loop region were associated with anxiety in patients with SLE (PBH = 0.001; PBH = 0.003). Associations of mtDNA CNVs with depression and anxiety in SLE were observed in several subgroups (Padj < 0.05). T9950C and T16140C variants were related to the improvement of anxiety in SLE (PBH < 0.05). An inverse U-shaped non-linear association was observed between mtDNA CNVs and the improvement of anxiety in the body mass index (BMI) ≥ 24 subgroup of SLE (Pnon-linear = 0.038). The levels of ROS (p = 0.040) and IL-6 (p = 0.039) were increased and ATP level (p = 0.034) was decreased in the COX3 gene variation group.

CONCLUSION

mtDNA genetic variants may be associated with depression and anxiety in Chinese patients with SLE. This study provides a new idea for improving depression and anxiety in SLE.