. 2020 Mar 12;15(3):e0230195. doi: 10.1371/journal.pone.0230195

Table 3. Influence of single nucleotide polymorphisms on TAC pharmacokinetics in whole blood and in PBMC.

Genotype	Allelic status	n	(%)	Tac AUC_{0-12h WB}	Tac AUC_{0-12h PBMC}	AUC_{0-12h PBMC}/	Tac C_{0 WB}	Tac C_{0 PBMC}	Tac C_{max WB}	Tac C_{max PBMC}
Genotype	Allelic status	n	(%)	(ng.h/mL)	(pg.h/million of PBMC)	AUC_{0-12h WB}	(ng/mL)	(pg/million of cells)	(ng/mL)	(pg/million PBMC)
Recipient ABCB1 3435C>T (rs1045642)	CC	2	(6)	132.2	769.1	27.4	6.7	49.9	19.4	101.2
				[101.4–162.9]	[411.1–1127.2]	[20.2–34.6]	[3.7–9.8]	[19.4–80.4]	[15.9–22.9]	[60.1–142.3]
	CT	21	(66)	99.7	548.8	24.3	6.2	30	15.3	71.3
				[35.0–215.5]	[223.0–1022.0]	[14.8–39.7]	[2.5–10.0]	[9.6–76.9]	[3.5–36.3]	[25.7–158.0]
	TT	9	(28)	103.1	486.6	19.2	6.2	23.2	18.3	74.9
				[75.1–163.8]	[295.7–1034.2]	[15.9–32.4]	[3.7–9.3]	[19.9–43.6]	[7.0–24.9]	[34.2–152.5]
Recipient ABCB1 1236 C>T (rs1128503)	CC	10	(31)	128.9	642	23.6	8.1	31.4	19.3	77.9
				[47.3–215.5]	[223.0–1127.2]	[14.8–35.6]	[3.7–9.8]	[9.6–80.4]	[5.9–36.3]	[25.7–156.8]
	CT	15	(47)	89.7	491.6	26.7	6.5	29.2	11	62.8
				[35.0–154.2]	[238.9–1034.2]	[17.6–39.7]	[2.5–10.0]	[17.7–60.9]	[3.5–22.4]	[28.9–158.0]
	TT	7	(22)	111.8	447.4	18.3	5.4	23.9	18.1	71.3
				[92.4–158.1]	[295.7–769.5]	[15.9–24.8]	[3.7–10.0]	[19.9–58.2]	[14.9–24.9]	[34.2–101.7]
Recipient ABCB1 2677 G>T/A (rs2032582)	GG	11	(34)	114	623.9	23.6	7.8	23.2	18.3	77
				[47.3–215.5]	[223.0–1127.2]	[14.8–35.6]	[3.7–9.8]	[9.6–80.4]	[5.9–36.3]	[25.7–156.8]
	GT	15	(47)	89.7	514.2	26.7	6.5	32.1	11.2	69.4
				[35.0–158.1]	[238.9–1034.2]	[20.0–39.7]	[2.5–10.0]	[17.7–60.9]	[3.5–22.4]	[28.9–158.0]
	TT	6	(19)	105.4	428.2	18.3	5.3	23.1	19.6	70
				[92.4–123.9]	[295.7–613.6]	[15.9–24.8] ^*	[3.7–6.2]	[19.9–43.9]	[17.5–24.9]	[34.2–101.7]
Recipient ABCB1 Haplotype 3435/1236/2177	Het TTT	17	(53)	99.1	514.2	25.1	6.2	32.1	14.9	69.4
				[35.0–158.1]	[238.9–1034.2]	[20.0–39.7]	[2.5–10.0]	[17.7–60.9]	[3.5–22.4]	[29.0–158.0]
	HomTTT	4	(13)	102.4	357.4	17.4	4.5	21.6	20.4	64.3
				[92.4–122.6]	[295.7–447.4]	[15.9–18.3] ^*	[3.7–6.2]	[19.9–23.9]	[17.5–24.9]	[34.2–82]
	Other	11	(34)	114	623.9	23.6	7.8	23.2	18.3	77.0
				[47.3–215.5]	[223.0–1127.2]	[14.8–35.6]	[3.7–9.8]	[9.6–80.4]	[5.9–36.3]	[25.7–156.8]
Recipient ABCB1 1199 G>A (rs2229109)	GG	29	(91)	99.7	486.6	23.1	6	23.9	17.5	69.4
				[35.0–163.8]	[223.0–1034.2]	[14.8–39.7]	[2.5–10.0]	[9.6–76.9]	[3.5–24.9]	[25.7–152.5]
	GA	3	(9)	162.9	1022	28	9.8	54.6	22.9	156.8
				[128.5–215.5]^*	[720.4–1127.2]^*	[23.7–34.6]	[9.6–10.0]^*	[39.3–80.4]^*	[19.9–36.3]^*	[142.3–158.0]^*
Recipient CYP3A4 (C>T) (*22, rs35599367)	CC	30	(94)	102.3	531.5	23.6	6.3	29.6	17.7	70.3
				[35.0–215.5]	[223.0–1127.2]	[14.8–39.7]	[2.5–10.0]	[9.6–80.4]	[3.5–36.3]	[25.7–158.0]
	CT	2	(6)	84.2	405.7	26.9	4.2	22.7	20.1	76.6
				[56.7–111.8]	[402.2–409.1]	[18.3–35.5]	[3.7–4.7]	[22.0–23.3]	[15.3–24.9]	[71.3–82.0]
Recipient CYP3A5 6986 G>A (*3, rs776746)	AA	32	(100)	102.3	502.9	23.6	6.2	28.4	17.7	71.3
Recipient CYP3A5 6986 G>A (*3, rs776746)				[35.0–215.5]	[223.0–1127.2]	[14.8–39.7]	[2.5–10.0]	[9.6–80.4]	[3.5–36.3]	[25.7–158.0]
Donor ABCB1 3435C>T (rs1045642)	CC	8	(25)	97.7	357.9	20.1	5.9	22.3	17.9	72.1
				[52.0–163.8]	[238.9–720.4]	[14.8–31.5]	[2.9–10.0]	[9.6–39.3]	[8.6–24.9]	[33.4–158.0]
	CT	12	(38)	96.1	453.7	24.3	5.1	28.5	15.6	71.3
				[35.0–158.1]	[277.6–1034.2]	[15.9–39.7]	[2.5–10.0]	[17.7–76.9]	[3.5–23.2]	[28.9–129.4]
	TT	12	(38)	120.3	581.2	24.2	7.2	34.8	19.9	74.2
				[47.3–215.5]	[223.0 1127.1]	[17.4–34.6]	[3.7–9.8]	[18.1–80.4]	[5.9–36.3]	[25.7–156.8]
Donor ABCB1 1236 C>T (rs1128503)	CC	11	(34)	111.7	514.2	23.0	5.8	23.9	18.3	74.9
				[35.0–163.8]	[238.9–813.0]	[14.8–39.7]	[2.5–10.0]	[9.6–76.9]	[3.5–24.9]	[28.9 158.0]
	CT	13	(41)	97.5	447.4	21.6	6.5	23.3	15.9	71.3
				[56.7–158.2]	[295.7–1034.2]	[15.9–35.5]	[3.7–10.0]	[18.1–58.2]	[7.0–23.3]	[40.5–152.5]
	TT	8	(25)	120.3	610.7	24.2	6.1	37.0	19.4	83.5
				[47.3–215.5]	[223.0–1127.2]	[21.1–38.6]	[3.7–9.8]	[19.2–80.4]	[5.9–36.3]	[25.7–156.8]
Donor ABCB1 2677 G>T/A (rs2032582)	GG	10	(31)	105.6	564.4	24.2	6.4	28.0	17.9	72.1
				[35.0–163.8]	[238.9–813.0]	[14.8–39.7]	[2.5–10.0]	[9.6–76.9]	[3.5–22.4]	[28.9–158.0]
	GT/A	11	(34)	97.48	411.1	20.1	4.9	22.2	17.6	74.9
				[56.7–143.8]	[295.7–1034.2]	[15.9–35.5]	[3.7–9.2]	[18.1–51.5]	[8.9–24.9]	[40.5–152.5]
	TT/A	11	(34)	123.9	607.8	24.3	7.0	43.6	18.1	65.4
				[47.3–215.5]	[223.0–1127.2]	[17.4–38.6]	[3.7–10.0]	[19.2–80.4]	[5.9–36.3]	[25.7–156.8]
Donor ABCB1 Haplotype 3435/1236/2177	HetTTT	14	(44)	98.3	473.3	23.2	5.8	28.5	16.8	68.3
				[56.7–158.2]	[295.7–1034.2]	[15.9–38.6]	[3.7–10.0]	[18.1–58.2]	[7.0–23.3]	[40.5–152.5]
	HomTTT	6	(19)	139.1	750.2	24.2	7.7	29.6	21.0	114.0
				[47.3–215.5]	[223.0–1127.2]	[21.1–34.6]	[3.7–9.8]	[19.2–80.4]	[5.9–36.3]	[25.7–156.8]
	other	12	(38)	105.7	461.7	23.0	6.1	23.2	17.9	72.1
				[35.0–163.8]	[238.7–813.0]	[14.8–39.7]	[2.5–10.0]	[9.6–76.9]	[3.5–24.9]	[28.9–158.0]
Donor ABCB1 1199 G>A (rs2229109)	GG	31	(97)	103.1	514.2	23.4	6.2	29.2	17.7	71.3
				[47.3–215.5]	[223.0–1127.2]	[14.8–38.6]	[3.0–10.0]	[9.6–80.4]	[5.9–36.3]	[25.7–158.0]
	GA	1	(3)	35.0 [n/a]	277.6 [n/a]	39.7 [n/a]	2.5 [n/a]	17.7 [n/a]	3.5 [n/a]	28.9 [n/a]
Donor CYP3A4 (C>T) (*22, rs35599367)	CC	27	(84)	99.7	491.6	24.5	6.2	29.2	17.5	71.3
				[35.0–162.9]	[223.0–1127.2]	[14.8–39.7]	[2.5–10.0]	[9.6–80.4]	[3.5–24.9]	[25.7–158.0]
	CT	5	(16)	158.2	548.8	20.3	8.5	23.4	18.3	74.9
				[89.7–215.5]	[411.1–1022.0]	[17.4–23.7]	[3.7–10.0]	[19.4–54.6]	[15.9–36.3]	[60.1–156.8]
Donor CYP3A5 6986 G>A (*3, rs776746)	Expressor GG and GA	2-Jan	(3)/(6)	103.1	447.4	18.3	4.8	19.9	23.2	77
				[95.8–122.6]	[283.7–623.9]	[14.8–30.3]	[3.8–4.9]	[9.6–23.2]	[20.2–23.3]	[74.9–152.5]
	Non expressor AA	29	(91)	101.44	514.2	23.6	6.5	30	17.5	69.4
				[35.0–215.5]	[223.0–1127.2]	[15.9–39.7]	[2.5–10.0]	[17.7–80.4]	[3.4–36.2]	[25.72–158.0]

AUC_0-12h: area under the concentration–time curve from 0h to 12h; PBMC: peripheral blood mononuclear cells; WB: whole blood; C₀: predose concentration; C_max: maximum concentration; Het: heterozygote; Hom: homozygote. Data are expressed as median [range]

* p<0.05.