Methylation levels and mRNA expression of ABCB1 in
relation to tacrolimus blood concentration
Through methylation chip screening, the methylation levels of
three ABCB1 sites
(cg12501229, cg00634941, and cg05496710) located on chromosome 7 were
found to be significantly different between the high and low tacrolimus
blood concentration groups (Figure 2A ). Using the
pyrophosphorylation assay, the
methylation levels of these three sites were further evaluated in the 23
donor liver specimens carrying the CYP3A5*3/*3 genotype. We found
that the methylation levels of these sites in the high
C0/D group were all significantly lower than those in
the low C0/D group (Figure 2B-D ).
Furthermore, ABCB1 mRNA expression levels were determined by
RT-qPCR, and correlation analyses
revealed that ABCB1 mRNA expression in donor livers was
positively correlated with the tacrolimus C0/D ratio (r
= 0.458, P < 0.05)
(Figure 3A ). An ABCB1 mRNA expression level of 0.15 was
used as the cut-off value to
analyse the tacrolimus
C0/D ratio and differences between the low-and
high-expression groups (Figure 3B and C ). Our results showed
that the greater proportion of patients with high blood tacrolimus
concentrations were found in the high ABCB1 expression group.