Abstract
Alu and LINE-1 elements are retrotransposons with a ubiquitous presence in the human genome that can cause genomic instability, specifically relating to telomere length. Genotoxic agents may induce methylation of retrotransposons, in addition to oxidative DNA damage in the form of 8-hydroxy-2′-deoxyguanosine (8-OHdG). Methylation of retrotransposons induced by these agents may contribute to biliary atresia (BA) etiology. Here, we investigated correlations between global methylation, 8-OHdG, and relative telomere length, as well as reporting on Alu and LINE-1 hypomethylation in BA patients. Alu and LINE-1 hypomethylation were found to be associated with elevated risk of BA (OR = 4.07; 95% CI: 2.27–7.32; P < 0.0001 and OR = 3.51; 95% CI: 1.87–6.59; P < 0.0001, respectively). Furthermore, LINE-1 methylation was associated with liver stiffness in BA patients (β coefficient = −0.17; 95% CI: −0.24 to −0.10; P < 0.0001). Stratified analysis revealed negative correlations between Alu and LINE-1 methylation and 8-OHdG in BA patients (P < 0.0001). In contrast, positive relationships were identified between Alu and LINE-1 methylation and relative telomere length in BA patients (P < 0.0001). These findings suggest that retrotransposon hypomethylation is associated with plasma 8-OHdG and telomere length in BA patients.
Highlights
Previous studies have highlighted relationships between global hypomethylation and several human diseases[10,11,12,13]
We further investigated whether Alu and LINE-1 methylation levels were associated with hepatic dysfunction, oxidative stress, and relative telomere length in Biliary atresia (BA) patients
Of 228 participants enrolled in this study, 114 patients were diagnosed with BA (57.89% female and 42.11% male) and 114 were healthy controls (56.14% female and 43.86% male)
Summary
Previous studies have highlighted relationships between global hypomethylation and several human diseases[10,11,12,13] Methylation of these elements makes them susceptible to oxidative stress[14], which may be a possible factor associated with biliary atresia. Alu and LINE-1 may be critical elements in chromosome and genomic stability and may be induced by an increase in oxidative stress, leading to genomic instability and DNA damage. As such, these elements may contribute to the pathophysiology of BA. Further understanding of global DNA methylation, oxidative damage, and telomere length would shed light on the role of epigenetic aberrations play in the etiology of BA and may support the development of effective strategies
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call