Mycophenolic acid AUC in Thai kidney transplant recipients receiving low dose mycophenolate and its association with UGT2B7 polymorphisms

Figures & data

Table 1 Demographic data of 138 patients who underwent pharmacokinetic study

Characteristics	Value (% or range)
Number of patients	138
Ethnicity: Thai	138 (100%)
Sex (n)
Male	83 (60.1%)
Female	55 (39.9%)
Age (years)	42±11 (31–53)
Body weight (kg)	64±13 (51–77)
Body surface area (m^2)	1.70±0.2 (1.5–1.9)
Donor source (n)
Deceased donor	62 (44.9%)
Living-related	76 (55.1%)
CNI (n)
CsA	75 (54.3%)
TAC	63 (45.7%)
Serum Cr (mg/dL)	1.35±0.41
Calculated CCr (mL/min/1.73 m^2)	65.08±18.15
Serum albumin (g/dL)	4.46±0.3
WBC (cell/mm^3)	7,985±2,877
AST (IU/L)	21.4±7.49
ALT (IU/L)	23.51±3.16
Dose of MPA (n)
MMF 1,000 mg/d	106 (76.8%)
MPS 720 mg/d	32 (23.2%)
CsA dose (mg/d)	134.64 (50–350)
TAC dose (mg/d)	4.2 (1–14.5)
Prednisolone dose (mg/d)	5.11 (2.5–15)

Abbreviations: ALT, alanine transaminase; AST, aspartate transaminase; CCr, creatinine clearance; CNI, calcineurin inhibitor; Cr, creatinine; CsA, cyclosporine; MMF, mycophenolate mofetil; MPA, mycophenolic acid; MPS, extended release form of mycophenolate sodium; TAC, tacrolimus; WBC, white blood cells.

Figure 1 (A) Comparison of AUC decile distribution between patients who carried TC alleles (dark bars) and patients who carried TT alleles (light bars) in UGT2B7 at position 268. (B) Comparison of allele frequency between the group with AUC above 30 mg-h/L (left pie chart) and the group with AUC below 30 mg-h/L (right pie chart).

Abbreviation: AUC, area under the curve.

Table 2 Test for association between polymorphisms and AUC

Polymorphism	Allele frequency of control group*	Allele frequency of case group*	Allele frequency difference	Heterozygous vs homozygous	Commonodds ratio
UGT2B7 −824G/A	GG =3 (5.14) GA =27 (22.73) AA =23 (25.14)	GG =4 (3.81) GA =28 (28.38) AA =53 (52.81)	OR =1.699 (P=0.04389) (95% CI 1.012–2.853) for G > A	OR =0.451(P=0.01968) (95% CI 0.230–0.885) for AA > GA	OR =0.604 (P=0.03674) for A > G
UGT2B7 H268Y (T/C)	TT =22 (23.78) TC =27 (23.44) CC =4 (5.78)	TT =53 (52.81) TC =28 (28.38) CC =4 (3.81)	OR =1.820 (P=0.02190) (95% CI 1.087–3.046) for C > T	OR =0.435 (P=0.01535) (95% CI 0.221–0.857) for TT > TC	OR =0.557 (P=0.01858) for T > C
UGT1A8 A173G (C/G)	CC =20 (18.72) CG =23 (25.55) GG =10 (8.72)	CC =24 (23.82) CG =42 (42.35) GG =19 (18.82)	OR =1.277 (P=0.29474) (95% CI 0.808–2.017) for C > G	OR =1.509 (P=0.27077) (95% CI 0.725–3.141) for CC > CG	OR =1.247 (P=0.30744) for C > G

Note:

* Expected allele frequencies in Hardy–Weinberg equilibrium were shown in parenthesis.

Abbreviations: AUC, area under the curve; CI, confidence interval; OR, odds ratio.