Reduced leukocyte mitochondrial DNA copy number is associated with relative telomere length and oxidative DNA damage in biliary atresia patients

Abstract

Objective: Mitochondrial dysfunction has been shown to be involved in the pathophysiology of biliary atresia (BA); however, the mechanism has yet to be elucidated. There has been no study regarding the possible relationships between relative telomere length, oxidative DNA damage in the form of 8-hydroxy-2′-deoxyguanosine (8-OHdG), and mitochondrial function in BA patients. We therefore investigated associations between mitochondrial DNA (mtDNA) copy number, relative telomere length, and 8-OHdG in peripheral blood leukocytes of BA patients. Methods: A total of 228 subjects (114 BA patients and 114 age-matched healthy controls) were enrolled in this case-control study. The mtDNA copy number, relative telomere length, and plasma 8-OHdG were measured. Results: The mtDNA copy number was significantly lower in BA patients than controls (p=0.0015). Furthermore, short telomere length and elevated plasma 8-OHdG were observed in BA patients (p<0.0001). Stratified analysis showed that mtDNA copy number was inversely associated with relative telomere length in BA patients (r=-0.49, p<0.0001), whereas mtDNA copy number in BA children revealed a positive correlation with 8-OHdG (r=0.31, p=0.001). Additionally, there was a negative correlation between mtDNA copy number and age in BA patients (r=-0.32, p=0.001). Conclusions: Decreased mtDNA copy number in BA patients was associated with relative telomere length and plasma 8-OHdG. These findings suggest that mtDNA copy number could be used as a biomarker for predicting cellular damage in post-operative BA patients; however, the prognostic role of mtDNA copy number in BA remains to be established in a longitudinal study.