title: Global methylation, oxidative stress, and relative telomere length in biliary atresia patients.
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.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
authors.forename: Wanvisa
authors.initials: W
authors.lastname: Udomsinprasert
authors.affiliation: Department of Oral and Biology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand.
authors.forename: Nakarin
authors.initials: N
authors.lastname: Kitkumthorn
authors.affiliation: Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Apiwat
authors.initials: A
authors.lastname: Mutirangura
authors.affiliation: Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
authors.forename: Voranush
authors.initials: V
authors.lastname: Chongsrisawat
authors.affiliation: Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
authors.forename: Yong
authors.initials: Y
authors.lastname: Poovorawan
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
authors.forename: Sittisak
authors.initials: S
authors.lastname: Honsawek
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D020087:Alu Elements; D017734:Bile Ducts, Extrahepatic / Q000378:metabolism / Q000473:pathology; D001656:Biliary Atresia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D004249:DNA Damage; D019175:DNA Methylation; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D018384:Oxidative Stress; D012306:Risk; D016615:Telomere / Q000737:chemistry*; D059505:Telomere Homeostasis; D014430:Twins, Monozygotic
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine