Patients
Of the 68 included patients, 12 (17.7%) were ABCG2 c.421C>A variant allele carriers and 56 were wt subjects (Table 1). Variants in CYP3A4 and CYP3A5 were rare (Table 1). The UGT1A9 -275T>A and UGT1A9 -2152C>T SNPs were in complete LD (Table 1). Consequently, patients were considered as having a wt or a variant diplotype. The three ABCB1 SNPs (Table 1) were in a strong LD (pairwise D’=0.85-0.95, r2=0.615-0.687). Therefore, patients were categorized in respect to the number of variant alleles : (i) all three genotypes are wt, or one is heterozygous (none or one variant allele); (ii) two to three variant alleles (any two or all three loci are heterozygous; or one variant homozygous and one heterozygous locus); (iii) four to six variant alleles. Variant carriers prevailed regardingUGT2B7 -161 C>T SNP, while wt homozygotes prevailed regarding SLC01B1 521T>C and ABCC2 -24C>T and ABCC2 1249G>A SNPs (Table 1). In respect to these SNPs, patients were categorized as variant carriers or as wt homozygotes.
Characteristics of ABCG2 c.421C>T variant carriers and wt controls are summarized in Table 2 and Figure 1A summarizes their (dose-adjusted) MPA concentration-time profiles over the dosing interval.