Low heritability in pharmacokinetics of talinolol: a pharmacogenetic twin study on the heritability of the pharmacokinetics of talinolol, a putative probe drug of MDR1 and other membrane transporters

Table 4 Influence of genetic polymorphisms in genes coding for efflux transporters on talinolol clearance

Gene	Genetic polymorphism	Variant	Genotype frequency (n) [%]	Clearance [l/min]
MDR1	C1236T	C/C	31 (34)	0.77 ± 0.28
	rs1128503	C/T	47 (52)	0.96 ± 0.37^a
		T/T	21 (24)	1.11 ± 0.50^a
	G2677T/A	G/G	29 (32)	0.77 ± 0.29
	(Ala893Ser/Thr)	G/T	47 (52)	0.96 ± 0.37^b
	rs2032582	T/T	20 (22)	1.14 ± 0.50^b
		G/A	2 (2)	0.74 ± 0.03
		A/A	0 (-)	-
		T/A	2 (2)	0.75 ± 0.10
	C3435T	C/C	19 (21)	0.83 ± 0.28
	rs1045642	C/T	62 (68)	0.97 ± 0.44
		T/T	19 (21)	0.92 ± 0.30
MDR5	C392T (Thr131Ile)	C/C	89 (98)	0.92 ± 0.37
	rs17143212	C/T	11 (12)	1.07 ± 0.54
		T/T	0 (-)	-
MRP2	-C24T	C/C	73 (80)	0.92 ± 0.39
	rs717620	C/T	21 (23)	1.03 ± 0.41
		T/T	6 (7)	0.73 ± 0.33
	G1249A (Val417Ile)	G/G	68 (75)	0.95 ± 0.41
	rs2273697	G/A	30 (33)	0.89 ± 0.37
		A/A	2 (2)	0.97 ± 0.05
ABCG2	G34A (Val12Met)	G/G	96 (105)	0.94 ± 0.40
	rs2231137	G/A	4 (5)	0.84 ± 0.25
		A/A	0 (-)	-
	C421A (Gln141Lys)	C/C	75 (82)	0.94 ± 0.37
	rs2231142	C/A	25 (28)	0.91 ± 0.46
		A/A	0 (-)	-

Data are given in mean ± standard deviation. ^aThere were significant differences between heterozygous (C/T) and homozygous (T/T) carriers of the MDR1 1236 T allele and homozygous carriers of the 1236C allele (C/C) as tested with the Jonckheere–Terpstra test (p = 0.0025). ^bThere were significant differences between heterozygous (G/T) and homozygous (T/T) carriers of the MDR1 2677 T allele and homozygous carriers of the 2677G allele (G/G) as tested with the Jonckheere–Terpstra test (p = 0.0015). Significance was determined after correction for multiple testing for p < 0.005 (Bonferroni correction)

ISSN: 1756-994X