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Updated: Mar 14, 2026

Sample Preparation to Bioinformatics Analysis of DNA Methylation: Association Strategy for Obesity and Related Trait Studies
Published on: May 6, 2022
Combined Influence of Genetic Polymorphism and DNA Methylation on ABCB1 Expression and Function in Healthy Chinese
Lan-Xiang Wu1, Hong-Bo Zhao2, Chun-Jie Wen3
1Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, People's Republic of China. lxwu2008@126.com.
Background And Objectives:
It is well known that the expression and function of ATP-binding cassette transporter B1 (ABCB1) show high interindividual variability, but the reasons have not yet been fully elucidated. In this study, combined influence of genetic polymorphism and DNA methylation on ABCB1 mRNA expression and digoxin pharmacokinetics in healthy Chinese males was analyzed.
Methods:
A total of 93 subjects who were homozygous for the ABCB1 1236-2677-3435 TTT or CGC haplotype were enrolled in this study. DNA methylation status of the ABCB1 promoter and ABCB1 mRNA expression level in exfoliated intestinal epithelial cells were analyzed using bisulfite sequencing PCR and real-time PCR. The pharmacokinetics of digoxin in subjects were investigated after administration of a single oral dose of digoxin 0.5 mg.
Results:
The DNA methylation levels of ABCB1 promoter showed no significant difference between TTT/TTT and CGC/CGC carriers (P = 0.54). Subjects with TTT/TTT haplotype pair and high methylation status (TTT/TTT-HM) showed a significantly lower ABCB1 mRNA level compared to other subjects. Compared with TTT/TTT-HM subgroup, the area under the plasma concentration-time curve from time zero to 72 h (AUC0-72) of digoxin was decreased by 26.9 %, the maximum plasma concentration (C max) was decreased by 25 % and the apparent oral clearance (CL/F) was increased by 21.2 % in CGC/CGC-LM subgroup. The values of time to maximum concentration (t max) and terminal elimination half-life (t 1/2) showed no significant difference.
Conclusions:
Both genetic polymorphism and DNA methylation variation should be taken into consideration to explain the interindividual variability in ABCB1 expression and function more clearly.
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