Effect of ABCG2 c.421C>A variant on exposure to MPA
In estimating the effect of ABCG2 c.421C>A variant,
we controlled for a number of potentially interfering factors (Table 3).
Before matching, variant and wt patients differed considerably in
respect to most of the matching variables (Table 4), while total
exposure (AUCτ,ss) appeared higher and total body
clearance (CLT/F,ss) appeared lower in variant carriers
than in wt controls (Table 4). Frequentist and Bayesian estimates
suggested by 45% (95%CI 10-92) and by 38% (95%CrI 7-81) higher total
exposure, respectively (Table 5), and by 34% (10-52) and 29% (5-47)
lower total body clearance, respectively (Table 5) in variant carriers
than in wt controls. Eventually, 11/12 variant carriers were matched to
43/56 wt controls with excellent balance regarding most matching
covariates except (d ≥0.1) for the donors’ ABCC2 1249
G>A genotype, body mass index and estimated creatinine
clearance (Table 4): average concentration-time profiles were not much
changed vs. raw data (Figure 1B), AUCτ,ss was still
higher (d=0.824) and CLT/F,ss was lower (d=-0.559) in
variant carriers than in wt controls (Table 4). With additional
adjustment for suboptimally matched covariates, frequentist and Bayesian
estimates indicated by 41% (95%CI 11-79) and by 39% (95%CrI 5-81),
respectively, higher total exposure, and by 27% (7-42) and by 29%
(5-46) lower total body clearance, respectively, in variant carriers
than in wt controls (Table 5). Probability that the GMR for
AUCτ,ss was >1.20 was 90.7% based on the
frequentist analysis and it was 85.6% based on the Bayesian analysis
(Figure 2).