Supplementary Tables
Impact of Genetic Polymorphisms of ABCB1 (MDR1, P-glycoprotein) on Drug
Disposition and Potential Clinical Implications: Update of the Literature
Clinical Pharmacokinetics
Stefan Wolking,1 Elke Schaeffeler,2,3 Holger Lerche,1 Matthias Schwab,2,4# Anne T. Nies2,3
1 Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of
Tübingen, Hoppe-Seyler Strasse 3, 72076 Tübingen, Germany
2 Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstr. 112, 70376 Stuttgart, Germany
3 University of Tübingen, Germany
4 Department of Clinical Pharmacology, University Hospital Tübingen, Auf der Morgenstelle 8, 72076
Tübingen, Germany
#
Corresponding author
Email: Matthias.Schwab@ikp-stuttgart.de
Tel: +49 711 8101 3700
Fax: +49 711 85 92 95
1
Supplementary Table 1 Extended list of effects of ABCB1 polymorphisms on pharmacokinetics
Haplotypes
Other SNPs
C3435T
Doxorubicin
G2677T/A
Anticancer
Docetaxel
C1236T
Drug
Analgetic
Fentanyl
Methadone
Kim et al. [1]
Levran et al. [2]
X
X
X
X
X
X
196 patients, post-op
11,15,33 109 former heroin addicts
44,47,48
Korean
Jewish
ancestry
D
D
Fajac et al. [3]
X
X
X
X
8,10
86 patients, breast cancer
Mixed
AUC
Kim et al. [4]
X
X
X
216 patients, breast cancer
Korean
Lal et al. [5]
X
X
X
62 patients, advanced breast
cancer
151 patients, breast cancer
Asian
Article
Voon et al. [6]
X
X
51
No. of patients
Ethnicity
Parameters
Effect
NS
1236TT/2677TT/3435TT:  D
Asian
Erlotinib
Fukudo et al. [7]
X
X
X
88 patients, NSCLC
Japanese
Imatinib
Gurney et al. [8]
X
X
X
UK
Irinotecan
Han et al. [9]
Zhou et al. [10]
X
X
X
X
X
X
Paclitaxel
de Graan et al. [11]
22 patients, gastrointestinal
tumor
107 patients, NSCLC
29 patients, nasopharyngeal
carcinoma
261 cancer patients
Caucasian
Japanese
X
Fransson et al. [12]
Green et al. [13]
Jiko et al. [14]
X
X
X
X
X
X
33 patients, gynecological
cancer
38 patients, ovarian cancer
X
X
16 patients, urogenital
Korean
Asian
mainly
Caucasian
Caucasian
3435TT:  AUC in premenopausal
women
AUC, AE, OS 3435TT:  OS,  AUC for
docetaxel,  neutropenia for
docetaxel
CL, Cmax,
1236CC/2677GG/3435CC:  AUC,
AUC
Cmax,  CL
AUC, CL,
2677T:  CL; rs2235047G: 
Cmax, t1/2, OS, neutrophils,  OS
PFS,
neutrophil
count
C0, CL,
NS
response, AE
CL/F
1236TT, 2677TT, 3435TT:  CL/F,
 toxicity-related dose reduction
AUC, CL
2677TT/3435TT:  AUC
Cmax, AUC,
3435CC:  Cmax
CL, t1/2
CL, AUC,
NS
Cmax, C0,
response, AE
CL
2677TT:  CL
AUC, Cmax,
CL, AE
CL, C0/D
2677GA:  CL
NS
2
cancer
Nakajima et al. [15]
Sissung et al. [16]
X
X
X
X
X
X
Sunitinib
Vincristine
Mizuno et al. [17]
Guilhaumou et al.
[18]
X
X
X
X
X
X
Bicalutamide
Antiepileptic
Carbamazepine
Kim et al. [19]
X
X
X
Meng et al. [20]
Ozgon et al. [21]
Puranik et al. [22]
X
X
X
X
X
X
X
X
Seo et al. [23]
X
X
X
X
Zhu et al. [24]
Kang et al. [25]
Lovric et al. [26]
X
X
X
X
X
Gabapentin
Lamotrigin
Phenobarbital
Basic et al. [27]
X
X
Phenytoin
Valproate
Ponnala et al. [28]
Turgut et al. [29]
X
Putnam et al. [36]
X
X
X
X
X
26 patients, advanced solid
tumors
19 patients, renal carcinoma
20 children, solid tumor
X
Japanese
Caucasian
AUC
AUC, t1/2,
3435T:  AUC
2677T, 3435T:  neutrophils
Japanese
Caucasian
AUC24, AUC4
C, C
intracellular,
AE
C
NS
NS
27 healthy subjects
Korean
41,45
84 patients, epilepsy
97 patients
90 patients, epilepsy
Chinese
Turkish
Mixed
8
210 patients, epilepsy
Japanese
210 patients, epilepsy
30 healthy subjects
222 patients, epilepsy
Chinese
Korean
Caucasian
60 patients, generalized
epilepsy
127 patients, epilepsy
104 patients, bipolar
disorder
Caucasian
Mixed
Turkish
C0
3435TT:  C0
C0/D, response NS
CL, t1/2
1236T:  CL (in African
Americans)
CL/F,
2677TT, 3435TT,
responder
1236T/2677T/3435T:  resistance
status
C0/D
3435CT:  C0/D
Cmax, AUC, t1/2 NS
C0, C0/D
1236CC, 1236C/2677G/3435C: 
C0/D
CSF
3435CT, 3435TT:  CSF C
concentration
C0
3435CC: lower C0
C0
NS
X
74 HIV patients
Caucasian
C0
3435CC:  C0
X
118 HIV patients
Caucasian
C0
3435T:  C0
35 HIV patients
20 Healthy subjects
18 healthy subjects
11 patients, cystic fibrosis/
11 controls
18 healthy subjects
Caucasian
Chinese
Chinese
Caucasian
C0
Cmax
CL, C0, Cmax
CL
2677GG:  C0
2677TT/3435TT:  Cmax
1236CC:  C0 ,Cmax
3435TT:  CL
Caucasian
Cmax, AUC,
CL
NS
X
X
X
Antiinfectious
Atazanavir
Rodriguez-Novoa et
al. [30]
Rodriguez-Novoa et
al. [31]
Atazanavir/Ritonavir D’Avolio et al. [32]
Azithromycin
He et al. [33]
Cloxacilline
Yin et al. [34]
Dicloxacilline
Beringer et al. [35]
8
X
X
X
X
X
X
NS
3
Efavirenz
Elens et al. [37]
Mukonzo et al. [38]
X
X
Mukonzo et al. [39]
Ngaimisi et al. [40]
Efavirenz/ Lopinavir Winzer et al. [41]
Efavirenz/
Fellay et al. [42]
Nelfinavir
Indinavir
Curras et al. [43]
Saquinavir
Valacyclovir
Antipsychotic
Clozapine
Olanzapine
Levisulpiride
Risperidone
African
African
Caucasian
Caucasian
CL/F, F, AUC
C0
C12, C0
C0
c.*193G:  F
c.*193G:  C0
NS
3435TT:  C0
C0, CL, C0/D
3435CC:  C0/D
28 HIV patients
South
American
Caucasian
103 HIV patients
Mixed
113 HIV patients
28 HIV patients
Brazilian
Caucasian
152 HIV-infected children
8 healthy subjects
Mixed
Caucasian
X
200 healthy subjects
X
12,20,21, 121 healthy subjects
23,26,28,
30,36,38,
53
53
99 HIV patients
53
494 HIV patients
43/ 32 HIV patients
69/ 54 HIV patients
X
X
X
X
X
X
X
X
X
X
X
Saitoh et al. [48]
Frohlich et al. [49]
X
X
X
X
X
Zhang et al. [50]
X
X
X
Consoli et al. [51]
Ghotbi et al. [52]
Cho et al. [53]
Gunes et al. [54]
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Jovanovic et al. [55]
Kastelic et al. [56]
Xiang et al. [57]
F
1
X
X
X
X
Solas et al. [44]
Lopinavir/
Ma et al. [45]
Atazanavir
Lopinavir/ Ritonavir Estrela et al. [46]
Nelfinavir
Colombo et al. [47]
African
c.*193G:  accumulation in
peripheral mononuclear cells
c.*193G:  F
X
X
50 HIV patients
21 HIV-infected children
X
X
X
Caucasian
C0, CL,
3435CT vs CC:  absorption rate
absorption rate constant
constant
C0
NS
NS
3435TT:  cellular AUC
Chinese
C0
cellular C,
AUC
CL/F
AUC, Cmax,
tmax, t1/2, CL
AUC, Cmax
X
60 patients, psychosis
121 schizophrenic patients
58 healthy subjects
46 patients, schizophrenia
Caucasian
Caucasian
Korean
Caucasian
D, C0
AUC
AUC, Cmax
C0/D
X
83 patients, psychosis
Caucasian
C0/D, side
effects
59 patients, psychosis
23 healthy subjects
Caucasian
Chinese
C0, response
Cmax, tmax,
AUC, CL/F,
t1/2
2677GG, 3545CC:  C0,  D
NS
2677TT, 3435TT:  AUC,  Cmax
1236T/2677T/3435T:  C0/D of 9'hydroxyrisperidone
2677TT, 3435TT:  C0/D;
2677TT/3435TT:  extrapyramidal
side effects
NS
2677GA:  tmax
23
NS
NS
NS
4
Quetiapine
Cardiac
Amlodipine
Yasui-Furukori et al.
[58]
Bakken et al. [59]
X
Kim et al. [60]
X
Aarnoudse et al. [62]
X
85 schizophrenic patients
Japanese
C0
NS
289 schizophrenic patients
Caucasian
C0/D
NS
X
26 healthy subjects
Korean
Chinese
2677TT/3435TT:  AUC, Cmax, 
CL/F
3435TT:  CL/F
X
60 patients; essential
hypertension
195 patients, digoxin user
CL/F, AUC,
Cmax
CL/F, AUC
Caucasian
C0
50 healthy subjects
Caucasian
AUC4, Cmax,
tmax
AUC4, Cmax
1236T, 2677T, 3435T,
1236T/2677T/3435T:  C0
NS
X
Zuo et al. [61]
Digoxin
X
X
X
X
X
Gerloff et al. [63]
X
X
Johne et al. [64]
X
X
X
24 healthy subjects
Caucasian
Kurata et al. [65]
Verstuyft et al. [66]
Verstuyft et al. [67]
X
X
X
X
X
X
15 healthy subjects
32 healthy subjects
12 healthy subjects
Japanese
Caucasian
Caucasian
X
X
X
20 healthy subjects
Chinese
58 healthy subjects
19 healthy subjects
Turkish
Chinese
Xu et al. [68]
X
23
Losartan
Telmisartan
Yasar et al. [69]
Guo et al. [70]
Verapamil
Pan et al. [71]
X
X
X
10 healthy subjects
Korean
Zhao et al. [72]
X
X
X
24 healthy subjects
Chinese
X
X
X
81 renal recipients
D, C0/D
2677GG, 2677G/3435C:  C0/D
42 liver recipients
mainly
Caucasian
Caucasian
C0/D
103 renal recipients
70 renal recipients
29 healthy subjects
Chinese
Korean
Korean
65 cardiac recipients
Caucasian
D, AUC12/D
C0
Cmax, AUC12,
tmax, t1/2
D
3545TT:  C0/D 1-3 days post
transplantation, not beyond
NS
NS
NS
150 liver recipients
Caucasian
C0/D, C0, C
Immunosuppressants
Tacrolimus
Anglicheau et al. [73]
Bonhomme-Faivre et
al. [74]
Cheung et al. [75]
Cho et al. [76]
Choi et al. [77]
Diaz-Molina et al.
[78]
Elens et al. [79]
X
X
3435TT:  Cmax, AUC4;
2677G/3435T:  AUC
CL, F
2677TT/3435TT:  CL,  F
AUC4, AUC24 3435TT:  AUC4,  AUC24
AUC4, AUC24, 3435TT:  AUC4,  AUC24
CL, Cmax
AUC4, Cmax,
1236TT/2677TT/3435TT:  AUC4,
tmax
 Cmax,  tmax
urine C
NS
Cmax, tmax, t1/2, NS
AUC, CL
AUC, Cmax,
NS
tmax
Cmax, CL,
2677TT/3435TT:  AUC
AUC
X
8
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
10,23
NS
1199A, 1236CC, 2677GG:  C
5
206 renal recipients
103 renal recipients
98 liver recipients
Mixed
Caucasian
Caucasian
liver
C0/D
D, CL/F, C0
C0, C0/D, D
liver
2677GG, 3435CC:  C0/D
NS
NS
Japanese
Japanese
C0/D
C0/D
NS
NS
Mixed
C0, AUC
NS
X
69 liver recipients
181 liver recipients, 114
donors
19 renal transplant
candidates
51 paediatric liver recipients
Caucasian
D
X
136 renal recipients
mainly
Caucasian
Japanese
G2677TT, 3435TT,
1236T/2677T/3435T:  D
NS
D, C0, C0/D,
acute rejection
C0/D
NS
Korean
C0
Caucasian
Fredericks et al. [80]
Gervasini et al. [81]
Gomez-Bravo et al.
[82]
Goto et al. [83]
Goto et al. [84]
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Haufroid et al. [85]
X
X
X
Hawwa et al. [86]
X
X
Hesselink et al. [87]
Hosohata et al. [88]
X
X
Jun et al. [89]
X
X
Kuypers et al. [90]
X
X
Kuypers et al. [91]
Li et al. [92]
X
X
X
X
Li et al. [93]
X
X
López-Montenegro et
al. [94]
MacPhee et al. [95]
MacPhee et al. [96]
Mai et al. [97]
Min et al. [98]
Mourad et al. [99]
X
X
Op den Buijsch et al.
[100]
X
X
X
63 living-donor liver
recipients
506 liver/ renal recipients,
62 donors
95 renal recipients
NS
Caucasian
Chinese
Chinese
D, C0/D
NS
X
304 renal recipients
73 liver recipients, 73
donors
70 liver recipients, 70
donors
35 renal recipients
C0/D,
NS
AUC12/D,
nephrotoxicity,
acute
rejection,
survival.
D, AUC, C0
NS
CL/F
NS
Caucasian
C0/D
3435CC:  C0/D
X
180 renal recipients
178 renal recipients
73 renal recipients
62 renal recipients
59 renal recipients
C0/D
C0, C0/D
C0/D
C0
D, C0/D
3435CC:  C0/D
NS
NS
NS
NS
X
63 renal recipients
Mixed
Mixed
Caucasian
Japanese
mainly
Caucasian
Caucasian
D, C0/D,
Cmax/D
NS
X
X
X
X
X
X
X
X
X
X
X
6
X
X
32 liver recipients
Caucasian
AUC12/D
D
NS
X
X
101 liver/ renal recipients
Caucasian
C0, D
2677T/A:  D
X
X
44 renal recipients
D, C0, C0/D
X
X
216 liver recipients
mainly
Caucasian
Chinese
-129C, 2677T, 3435T:  C0/D when
less than 3 copies of these SNPs
NS
Shilbayeh et al. [105]
X
38 renal recipients
Tada et al. [106]
X
39 renal recipients
Middle
Eastern
Japanese
X
X
30 renal recipients
Japanese
X
X
X
Caucasian
Chinese
Provenzani et al.
[101]
Provenzani et al.
[102]
Roy et al. [103]
X
Shi et al. [104]
Tsuchiya et al. [107]
Wang et al. [108]
Wei-lin et al. [109]
X
Zhang et al. [110]
Zheng et al. [111]
Tacrolimus/
Sirolimus
Mourad et al. [112]
X
Renders et al. [113]
Everolimus
Tacrolimus/
Cyclosporine
8,10
X
X
X
X
91 lung recipients
50 liver recipients, 50
donors
118 renal recipients
75 lung recipients
X
X
X
X
Lemaitre et al. [114]
Bandur et al. [115]
X
X
X
X
X
Haufroid et al. [116]
X
X
X
X
Hesselink et al. [117]
X
Loh et al. [118]
X
Onizuka et al. [119]
X
X
X
Singh et al. [120]
X
X
X
X
D, C0/D, early
renal injury
t to attain
target C
D, AUC12/D,
Cmax, tmax, t1/2,
CL/F
D, AUC12/D,
Cmax, Cmax/D,
tmax, t1/2, CL/F
C0/D
C0/D
NS
NS
NS
1236TT/2677TT/3435TT:  C0/D
3435CC:  C0/D
D, C0, C0/D
D, C0/D
NS
NS
24 renal recipients
Chinese
mainly
Caucasian
Caucasian
D, C0, C0/D
NS
134 renal recipients
Caucasian
NS
59 cardiac recipients
407 Cy, 425 Tac renal
recipients
50 Cy, 50 Tac renal
recipients
110 Cy, 64 Tac renal
recipients
64 Cy, 18 Tac renal
recipients
21 Cy, 37 Tac patients after
HCST
225 Cy, 75 Tac renal
Caucasian
Caucasian
Caucasian
D, C0, C0/D,
AUC12, AUC24
CL, CL/F
C0, C0/D,
rejection
D, C0, C0/D
Mixed
D, C0, C0/D
NS
Mixed Asian D, C0, C0/D,
C2
Japanese
NS
South Asian
2677GG, 3435CC:  C0/D
C0/D
NS
1236T/2677T/3435T:  risk of
rejection.
NS
NS
7
Cyclosporine
Anglicheau et al.
[121]
X
X
recipients
106 renal recipients
White
X
X
88 liver recipients
44 liver recipients
Iranian
Caucasian
171 renal recipients
Mixed
X
X
8
Azarpira et al. [122]
Bonhomme-Faivre et
al. [123]
Bouamar et al. [124]
X
X
X
Chowbay et al. [125]
X
X
X
X
Crettol et al. [126]
X
X
X
X
10,23
73 renal/ lung recipients
Fanta et al. [127]
X
X
X
X
23
104 renal recipients
Foote et al. [128]
Garcia et al. [129]
Hesselink et al. [130]
X
X
X
X
X
X
14 cardial recipients
C0, C2,
rejection, renal
function
Mixed Asian C0, Cmax,
AUC4, AUC12
Caucasian
D, C0, C0/D,
intracellular
concentration
mainly
D, CL, F
Finnish
X
X
X
X
X
X
X
X
Press et al.
X
X
X
X
Qiu et al. [135]
X
X
X
X
103 renal recipients
Caucasian
Caucasian
Mainly
White
Chinese
Japanese
Caucasian
mainly
African
American
mainly
Caucasian
Chinese
Taegtmeyer et al.
[136]
Wang et al. [137]
X
X
X
X
337 cardial recipients
Caucasian
C0
X
X
X
X
112 renal recipients
Chinese
C0/D
18 renal recipients
Mixed
Cmax/D,
AUC/D, tmax,
CL/F
Hu et al. [131]
Kuzuya et al. [132]
Mai et al. [133]
Min et al. [134]
Yates et al. [138]
X
X
75 renal recipients
68 renal recipients
151 cardial/ renal recipients
C0/D, Cmax/D,
AUC4/D,
AUC12/D, t1/2
D, C0, C0/D
D, C2, C2/D
8
X
8
106 renal recipients
97 renal recipients
98 renal recipients
16 healthy subjects
33 renal recipients
AUC4/D, C0
C0, AE
CL/F
1236C:  Cmax/D, AUC4/D
3435TT:  C0/D
3435TT:  D,  C2/D
NS
1236T/2677T/3435T:  AUC4, 
AUC12,  Cmax,  C0
3435T: 1.7-fold  intracellular C;
1199A: 1.8-fold  intracellular C
1236CC, 2677GG,
1199G/1236C/2677G/3435C: 
pre-hepatic ER,  F
3435T:  AUC4/D
3435:  nephrotoxicity
NS
D, C0, C0/D
AUC2
C0, C2, AUC12
tmax, Cmax, t1/2,
AUC, CL/F
3435C:  C0/D
NS
NS
NS
CL/F, AUC
NS
C0/D, C2/D
1236CC, 1236C/2677A/3435C: 
C0/D
1236CC, 12677GG, 3435CC:  C0
2677TT, 1236T/2677T/3435C: 
C0/D
3435T:  CL/F
8
Methotrexate
Budesonide
Kim et al. [139]
Dilger et al. [140]
Prednisolone
Platelet Inhibition
Clopidogrel
Miura et al. [141]
Statins
Fluvastatin/
Pravastatin/
Lovastatin/
Rosuvastatin
Miscellaneous
Fexofenadine
X
X
X
X
X
X
Frelinger et al. [142]
X
Taubert et al. [143]
X
Karazniewicz-Lada
[144]
X
Keskitalo et al. [145]
X
X
X
X
Drescher et al. [146]
Kim 2001 [147]
X
X
X
X
X
50
20 patients after HCST
21 patients, primary biliary
cirrhosis
95 renal recipients
Korean
Caucasian
CL
AUC, Cmax
3435CC,CT:  CL
NS
Japanese
Cmax, AUC24
NS
160 healthy subjects,
homozygous CYP2C19
60 patients, coronary artery
disease
42 patients undergoing
coronary angiography
Mixed
AUC, Cmax
NS
Caucasian
AUC, Cmax
3435TT:  Cmax,  AUC
Caucasian
AUC, Cmax
3435TT:  Cmax,  AUC
20 healthy subjects
Caucasian
AUC
NS
20 healthy subjects
healthy subjects
Caucasian
Caucasian
and AfricanAmerican
Japanese
Caucasian
AUCinf, Cmax
AUC, C0
NS
1236C/2677G/3435C:  AUC
Kodaira et al. [148]
X
15 healthy subjects
Cmax
3435TT:  Cmax
Pauli-Magnus et al.
X
16 healthy subjects
AUC, tmax
NS
[149]
Skarke et al. [150]
X X X
21 healthy subjects
Caucasian
AUC6
NS
Rebamipide
Cho et al. [151]
X X
30 healthy subjects
Korean
AUC, Cmax
NS
“X” denotes that this variant was tested. “Other SNPs” are found in supplementary Table 3. AE=adverse effects, AUC=area under concentration-time curve, AUCx=AUC from
time 0 to x, C=concentration, C/D=dose dependent C, C0=trough concentration, C0/D= dose dependent C0, Cmax=maximum concentration, CSF=cerebrospinal fluid,
Cx=concentration at time x, CL= apparent body clearance, CL/F=oral clearance, D=required dose, F=bioavailability, NS=not significant, OS=overall survival, PFS=progression
free survival, t1/2=elimination half time, tmax=time to Cmax,  increase,  decrease.
Lansoprazole
Loperamide
9
Supplementary Table 2 Extended list of effects of ABCB1 polymorphisms on pharmacodynamics
G2677T/A
C3435T
Haplotypes
Other SNPs
Morphine
C1236T
Drug
Analgetic
Methadone
Coller et al. [152]
X
X
X
X
10,23
Lotsch et al. [153]
X
X
X
60 patients, opioid
dependent
51 healthy subjects
X
145 patients
Caucasian
pupil size 9h after
administration
pain relief
74 patients, post-op
Caucasian
D, AE
References
Campa et al. [154]
Parameters
Effect
Australian
D
1236TT/2677TT/3435TT:  D
Caucasian
NS
X
X
X
X
X
X
X
X
X
X
X
X
X
Zwisler et al. [160]
X
X
33 healthy subjects
Caucasian
Zwisler et al. [161]
X
X
256 patients, postoperative pain
Gonzales-Haba et al. X
[162]
X
X
5-FU+ epirubicin+
cyclophosphamide
Cetuximab +
Irinotecan
Cisplatin
Vulsteke et al. [163] X
X
X
Docetaxel
Sissung et al. [166]
Anticancer
5-FU/ Capecitabine
Ross et al. [158]
Sia et al. [159]
Paule et al. [164]
X
Ethnicity
X
Oxycodon
Coulbault et al.
[155]
Fujita et al. [156]
Lotsch et al. [157]
No. of patients
8,20
X
Chen et al. [165]
X
X
X
X
X
8
X
3435 associated with pain relief
variability
2677GG/3435CC:  AE
1236TT, 2677TT/3435TT:  fatigue
3435TT:  D
Caucasian
AE
efficacy (24h-pain
score), AE, D
efficacy, AE
morphine
consumption, pain
scores, AE
efficacy (cold
pressor test), AE
pain relief (NRS)
141 patients, CRC
Caucasian
AE
991 patients, breast
cancer
23 patients, refractory
liver metastatic CRC
95 patients, NSCLC
Caucasian
survival
1236, 3435, 2677: altered risks of
AE: hand-foot syndrome,
leukopenia, diarrhea
2677GT:  survival
Caucasian
outcome
3435TT:  outcome
Chinese
response, AE
73 patients, androgen
independent prostate
mainly
Caucasian
OS
2677T:  resistance;
-129T/2677T/3435C:  response
1236C/2677G/3435C:  OS
32 cancer patients
Japanese
352 patients with chronic
pain
228 cancer patients
Caucasian
women after C-section
Chinese
2677G:  AE
NS
3435TT: less AE; 2677TT:  AE,
 efficacy
NS
10
Tsai et al. [167]
X
X
X
Choi et al. [168]
X
X
X
6,7
AE
92 patients, solid tumors
Koreans
AE, response
54 patients, SCLC
Japanese
response
2677GG:  fever,  febrile
neutropenia
3435TT:  neutropenia, anemia.
2677G/T:  leucopenia, 
resistance
3435CC, 2677G/3435C:  response
48 patients, pancreatic
cancer
46 patients, CML
Japanese
outcome, AE
NS
Caucasian
resistance
Caucasian
North
African
Chinese
Japanese
response, C0
response
1236TT, 1236CT, 2677TT, 3435TT:
 resistance
1236TT:  C0,  response
2677TT:  response
response
AE
1236TT, 3435TT:  resistance
3435TT:  diarrhea.
250 patients, metastatic
CRC
White
response, AUC
NS
109 patients, metastatic
breast cancer
43 patients, gastric
cancer
111 patients, breast
cancer
914 patients, ovarian
cancer
26 patients, advanced
solid tumor
51 patients, advanced
ovarian cancer
53 patients, ovarian
cancer
88 patients, renal
carcinoma
96 patients, renal
carcinoma
Korean
survival,
chemoresistance
PFS
3435CT:  survival. 2677GG: 
chemoresistance
3435TT:  PFS
NS
Caucasian
response,
neurotoxicity
response, AE
Caucasian
AE
NS
Caucasian
PFS
1199T/A:  PFS
Caucasian
response
2677TT, 2677TA:  response
mainly
Caucasian
mainly
Caucasian
PFS, OS
1236TT:  OS,  PFS
time to dose
reduction
1236TT:  time to dose reduction
Etoposide +
Cisplatin
Gemcitabine
Sohn et al. [169]
X
X
Kasuya et al. [170]
X
X
Imatinib
Deenik et al. [171]
X
X
X
Dulucq et al. [172]
Elghannam et al.
[173]
Ni et al. [174]
Lara et al. [175]
X
X
X
X
90 patients, CML
96 patients, CML
X
X
X
X
52 patients, CML
651 patients, SCLC
De Mattia et al.
[176]
X
X
X
X
Chang et al. [177]
X
X
X
Chang et al. [178]
X
X
Irinotecan +
Cisplatin
Irinotecan +
Leukovirin +
Cisplatin
Paclitaxel
Paclitaxel +
Carboplatin
Hertz et al. [179]
X
X
X
Marsh et al. [180]
X
X
X
Sissung et al. [16]
X
X
X
Green et al. [181]
X
Green et al. [182]
Sunitinib
Beuselinck et al.
[183]
Beuselinck et al
[184]
X
cancer
59 patients, breast cancer Chinese
8,16,22
23,27,29
X
23,25
X
X
X
X
X
X
X
X
Chinese
Mixed
NS
11
Garcia-Donas et al.
[185]
van Erp et al. [186]
X
X
X
X
X
X
Temozolomide
Schaich et al. [187]
X
X
X
Vinorelbin +
Cisplatin
Methotrexate
Doxorubicin+
vinvristine+
prednsisolone
Methotrexate
Antidepressant
Amitriptylin/
Citalopram/
Mirtazepine/
Paroxetin/
Venlafaxine
Pan et al. [188]
X
X
Citalopram
Karlsson et al. [192] X
X
X
101 patients, renal
carcinoma
219 patients, renal
carcinoma
119 patients,
glioblastoma
69 patients, NSCLC
Caucasian
AE, response
NS
Caucasian
AE
Caucasian
survival
Chinese
response
1236T/2677T/3435T:  hand foot
syndrome
1236CC:  survival, independent of
MGMT status
3435CC, 2677G/3435C:  response
Zgheib et al. [189]
Gregers et al. [190]
X
X
X
X
X
X
127 patients, ALL
522 patients, ALL
Lebanese
Danish
AE
AE
3435T and 1236T:  neutropenia
3435TT:  bone marrow toxicity
Gregers et al. [190]
X
X
X
522 patients, ALL
Danish
AE
3435CC:  liver toxicity
16,35,38
39,41-47
443 patients, major
depression
Caucasian
response (HAMD- 95 SNPs examined. Only SNPs with
17)
significant  response are listed. NS
for mirtazapine
23
112 forensic autopsy
cases positive for
citalopram
54 patients, major
depression
100 patients, major
depression
mainly
Caucasian
rate of lethal
intoxication
Turkish
response (HAMD- NS
17)
response (HAMD- rs1922242, rs1202184: association
17)
with severity of depressive
symptoms;
rs1882478/rs2235048/rs2235047
/rs1045642/rs6949448 (TTTCC): 
remission
response
1236T/2677G/3435C:  response
Uhr et al. [191]
X
Ozbey et al. [193]
X
X
Escitalopram
Lin et al. [194]
X
X
X
3-6,11,13
14,17-19
32,37,39
40,48,5052
Paroxetin
Kato et al. [195]
X
X
X
X
X
X
Paroxetin/
Mirtazepine
Mihaljevic et al.
[196]
Sarginson et al.
[197]
X
X
Venlafaxine
Karlsson et al. [192] X
X
X
Patients with major
depression
127 patients, major
depression
1,8-10,16
246 patients, major
22,23,26,27 depression
31,34,44
23
116 forensic autopsy
Chinese
Japanese
Caucasian
NS
mainly
Caucasian
response (HAMD- NS
17)
response (HAMD- Paroxetine: rs2032583C, 2235040A:
17)
earlier response; mirtazapine: NS
mainly
rate of lethal
1236CC+CT, 3435CC+CT: 
12
Fluoxetine
Gassó et al. [198]
Various drugs
Menu et al. [199]
Antiemetic
Domperidone
Granisetron/
Tropisetron/
Ondansetron
Granisetron +
Dexamethasone
Ondansetron
Ondansetron +
Metoclopramide
Ondansetron/
Granisetron
Antiepileptic
Carbamazepine
X
X
X
X
Caucasian
intoxication
intoxication
Caucasian
response (CGII)
2677TT:  response
Caucasian
response (HAMD- NS
17, BDI, CGII, TI)
48 patients, gastroparesis
216 cancer patients
Caucasian
Turkish
D
response (selfreport)
61G:  D
3435TT:  response
response (control
of emesis)
vomiting after
surgery
nausea, vomiting
2677TT:  response
response (control
of emesis)
3435TT:  response
Parkman et al. [200] X
Babaoglu et al.
[201]
X
X
X
Tsuji et al. [202]
X
X
64 patients, breast cancer Japanese
Choi et al. [203]
X
X
Korean
X
X
X
X
X
X
198 patients,
postoperative
202 patients, cisplatin
therapy
239 cancer patients
South
Asian
North
African
South
Asian
Turkish
responder status
2677TT:  response
X
314 patients, focal
epilepsy
100 patients, epilepsy
response
3435CC:  resistance
responder status
NS
resistant epilepsy
NS
Mixed
responder status
NS
Chinese
Caucasian
responder status
responder status
NS
NS
Mixed
responder status
NS
Mixed
responder status
NS
Asian
responder Status
Complex haplotypic effects
Perwitasari et al.
[204]
Zoto et al. [205]
Phenytoin
Subenthiran et al.
[206]
Ebid et al. [207]
Valproic acid
Haerian et al. [208]
Various drugs
Alpman et al. [209]
Bournissen et al.
[210]
Dong et al. [211]
Emich-Widera et al.
[212]
Haerian et al. [213]
10
cases positive for
venlafaxine
83 children and
adolescents
117 patients, major
depression
X
X
X
X
X
X
249 patients, epilepsy
X
X
X
39 children, epilepsy, 92
controls
3371 patients, epilepsy,
(MA)
350 children, epilepsy
85 patients, epilepsy
X
X
X
X
X
X
Haerian et al. [214]
X
X
X
X
Hung et al. [215]
X
X
X
X
6755 patients, epilepsy,
(MA)
7067 patients, epilepsy,
(MA)
331 patients, epilepsy,
287 controls
South
Asian
Turkish
2677TT, 3435TT:  vomiting 2h
post-op; NS 24h post-op
1236T/2677G/3435C:  response
13
Kwan et al. [216]
Leschziner et al.
[217]
Sanchez et al. [218]
Siddiqui et al. [219]
Antiinfectious
Atazanavir
Mefloquine
Nevirapine
Antipsychotic
Olanzapine
Risperidone
Colchicine
Cyclosporine
X
X
X
X
X
X
X
X
X
464 patients, epilepsy
503 patients, epilepsy
Chinese
UK
responder status
responder status
2677: related to drug resistance
NS
responder status
responder status
NS
3435CC:  resistance
responder status
NS
response
NS
2677TT:  severe
hyperbilirubinemia
1236TT, 2677TT, 3435TT,
1236TT/2677TT/3435TT:  AE
3435TT:  hepatotoxicity
3435T:  hepatotoxicity
Tan et al. [220]
X
289 patients, epilepsy
315 patients, epilepsy,
200 controls
609 patients, epilepsy
Manna et al. [221]
X
175 patients, epilepsy
Caucasian
mainly
Caucasian
mainly
Caucasian
Caucasian
X
X
129 HIV-patients
Korean
AE
X
X
89 healthy travelers
White
X
X
156 HIV-patients
53 HIV-patients
Caucasian
Mixed
neuropsychiatric
AE
hepatotoxicity
hepatotoxicity
X
X
X
X
87 schizophrenic patients Caucasian
41 schizophrenic patients Caucasian
X
X
X
X
X
X
X
X
X
X
Park et al. [222]
Aarnoudse et al.
[223]
Ciccacci et al. [224]
Haas et al. [225]
Bozina et al. [226]
Lin et al. [227]
X
X
Kuzman et al. [228]
Xing et al. [229]
Immunosuppressant
Azathioprine
X
X
X
Mendoza et al. [230]
Rustemoglu et al.
[231]
Saricaoglu et al.
[232]
Tufan et al. [233]
X
Grinyo et al. [234]
X
Hauser et al. [235]
van Ahsen 2001
[236]
X
X
48
X
X
X
X
X
X
X
10,53
108 schizophrenic
patients
130 schizophrenic
patients
Caucasian
response (PANSS) 2677T, 2677TT:  response
response (BPRS), NS
weight gain
weight gain
NS
Chinese
response (BPRS)
1236TT:  response
76 patients with Crohn's
disease
104 patients, Behcet's
disease
97 patients, Behcet's
disease
120 patients, familial
mediterranean fever
237 renal recipients
Brazilian
resistance
Turkish
response
2677TT, 3435TT, 2677T/3435T: 
resistance
3435TT:  response
Turkish
response
NS
Turkish
resistance
3435C:  resistance
Caucasian
graft rejection
97 renal recipients, 97
donors
124 renal recipients
Caucasian
C0/D, AE
2677T, 1236T/2677T/3435T: 
rejection
3435TT:  nephrotoxicity
Caucasian
graft rejection, C0
NS
14
Cyclosporine/
Tacrolimus
Methotrexate
Wang et al. [237]
X
Woillard et al. [238] X
X
X
X
X
X
Hebert et al. [239]
X
X
X
X
X
X
X
X
X
X
X
Klauke et al. [240]
Yamauchi et al.
[241]
Yanagimachi et al.
[242]
Zheng et al. [243]
Takatori et al. [244]
Samara et al. [245]
208 renal recipients
259 renal recipients, 227
donors
120 liver recipients
Chinese
Caucasian
response, AE
graft rejection
NS
1236T/2677T/3435T:  rejection
Caucasian
106 renal recipients
17 liver recipients
Caucasian
Japanese
chronic renal
dysfunction
nephrotoxicity
AE
2677TT:  risk; 2677G/3435C,
2677G/3435T:  risk
NS
2677TT:  neurotoxicity
Japanese
neurotoxicity
1236T neurotoxicity
X
X
X
30/ 33 patients after
HSCT
117 lung recipients
124 patients, RA
159 patients, RA
graft rejection
response, AE
response, AE
3435TT:  rejection
3435TT:  resistance
3435T:  hepatotoxicity
X
174/ 81 patients, RA
Mixed
Japanese
Middle
Eastern
Caucasian
remission
Methotrexate: 3435T:  remission
X
74 children, idopathic
nephrotic syndrome
31 children, ITP
Chinese
steroid resistance
1236T:  resistance
Turkish
response (platelet
count)
NS
1034 patients, coronary
DES
2208 patients, acute
myocardial infarction
Mixed
cardiovascular
event rate
death of any cause,
stroke or
myocardial
infarction
cardiovascular
events
early/ long-term
major
cardiovascular
events, platelet
activity
cardiac death,
recurrent infarction
platelet reactivity
(VASP-PRI)
ischemic events
NS
7,8,53
X
Methotrexate/
Sulfasalazine
Steroids
Drozdzik et al. [246]
Methylprednisolone
Akin et al. [248]
X
Platelet Inhibition
Clopidogrel
Carlquist et al. [249]
X
Simon et al. [250]
X
Singh et al. [251]
X
19601 patients
Mixed
Su et al. [252]
X
MA
Mixed
Verschuren et al.
[253]
Xie et al. [254]
X
1327 patients, STEMI
Caucasian
X
162 patients, coronary
heart disease
2932 patients, acute
Chinese
Clopidogrel/
Chiou et al. [247]
Mega et al. [255]
X
X
X
X
X
X
mainly
Caucasian
mainly
3435TT  cardiovascular events
NS
3435T,TT:  early/ long-term
events
NS
NS
Clopidogrel: 3435TT:  ischemic
15
Prasugrel
Clopidogrel/
Ticagrelor
Statins
Atorvastatin
Simvastatin
Wallentin et al.
[256]
X
coronary syndrome
10285 patients, acute
coronary syndrome
Caucasian
mainly
Caucasian
events
ischemic/ bleeding Clopidogrel: 3435CC:  ischemic
events
events
Hoenig et al. [257]
X
117 patients
Caucasian
Shabana et al. [258]
X
50 patients, high
cholesterol
North
African
85 patients, simvastatin
user
Caucasian
cholesterol
reduction
change of HDL-,
LDL-, total
cholesterol
cholesterol
reduction
Becker et al. [259]
X
X
X
X
3435CC:  efficacy in LDL-C
reduction
3435TT:  HDL-C
1236T/2677T/3435T,
1236C/2677G/3435T:  reduction
of total cholesterol and LDL-C male
subjects only
“X” denotes that this variant was tested. “Other SNPs” are found in supplementary Table 3. AE=adverse effects, ALL, acute lymphoblastic leukemia, AUC=area under the curve,
AUCx=AUC from time 0 to x, BDI=Becks Depression Inventory, BPRS=Brief psychiatric rating scale, C=concentration, C0=trough concentration, CGII=Clinician Global
Impression Improvement, CML=chronic myeloid leukemia, CRC=colorectal cancer, D=required dose, DES=drug eluting stent, HAMD-17=Hamilton Depression Rating Scale,
HDL-C=high density lipoprotein cholesterol, HSCT=hematopoietic stem cell transplantation, ITP=idiopathic thrombocytopenic purpura, LDL-C=low density lipoprotein
cholesterol, MA=metanalysis, NSCLC=non-small cell lung cancer, NRS=numeric rating scale, NS=not significant, OS=overall survival, PANSS=Positive and negative syndrome
scale, PFS=progression free survival, RA=rheumatoid arthritis, SCLC=small cell lung cancer, STEMI=ST-elevation myocardial infarction, TI=Therapeutic Index, VASP
PRI=platelet reactivity index VASP,  increase,  decrease.
16
Supplementary Table 3 List of ABCB1 SNPs investigated in pharmacogenetic studies
Position
Code
Amino acid or effect
rs10245483
approximately 2.4 mb upstream of MDR1
2.
n.a.
c.-330-14566G>A
rs13233308
Intron 1
3.
c.-330-1517T>C
rs28381796
Intron 1
4.
c.-330-21247T>C
rs1978095
Intron 1
5.
c.-330-3655A>G
rs4148732
Intron 1
6.
c.-330-41A>G
rs2188524
Intron 1
7.
c.-145C>G
rs34976462
5'UTR
8.
c.-129T->C
rs3213619
5'UTR
9.
c.-1A->G
rs2214102
5'UTR
10.
c.61A->G
rs9282564
Asn21Asp
11.
c.117+4196T>C
rs3789243
Intron 3
12.
c.239C→A
rs9282565
Ala80Glu
13.
c.286+927G>A
rs1202184
Intron 5
14.
c.287-1234G>C
rs10256836
Intron 5
15.
c.287-1547G>A
rs2520464
Intron 5
16.
c.287-25G>T
rs2235015
Intron 5
17.
c.287-5940A>T
rs1989831
Intron 5
18.
c.338+123A>G
rs2235018
Intron 6
19.
c.338+76T>G
rs2235016
Intron 6
20.
c.530+139C>T
rs1202168
Intron7
21.
c.781A→G
rs36008564
Ile261Val
22.
c.1000-44G>A
rs10276036
Intron 10
23.
c.1199G→A
rs2229109
Ser400Asn
24.
c.1236C→T
rs1128503
25.
c.1308A>G
rs35068177
Gly412=
Thr436=
26.
c.1350+44C>T
rs2032588
Intron 13
27.
c.1554+24T>C
rs2235033
Intron 14
28.
c.1659 G→C
rs2235012
Leu554Leu
29.
c.1725+38G>A
rs2235013
Intron 15
30.
c.1795C→T
rs2235036
Ala599Thr
31.
c.1887+38G>A
rs28381916
Intron 16
32.
c.2064+73A>G
rs2235046
Intron 17
33.
c.2065-76T>A
rs1922242
Intron 17
34.
c.2212-27A>G
rs2235063
Intron 18
35.
c.2320-695G>A
rs12720067
Intron 19
36.
c.2320-88G>A
rs4728699
Intron 19
37.
c.2397+557G>A
rs3789246
Intron 20
38.
c.2481+24G>A
rs2235040
Intron 21
39.
c.2481+788T>C
rs10248420
Intron 21
40.
c.2481+882A>T
rs10234411
Intron 21
41.
c.2482-236A>G
rs4148739
Intron 21
42.
c.2482-707A>G
rs11983225
Intron 21
43.
c.2677G→T/A
rs2032582
44.
c.2685+49T>C
rs2032583
Ser893Ala/Thr
Intron 22
1.
17
45.
c.2686-1911T>C
rs4148740
Intron 22
46.
c.2686-3393T>G
rs10280101
Intron 22
47.
c.2786+170G>A
rs2235067
Intron 23
48.
c.3282+2733A>G
rs6949448
Intron 26
49.
c.3435C→T
rs1045642
50.
c.3489+1573G>A
rs1882478
Ile1145=
Intron 27
51.
c.3489+59T>G
rs2235047
Intron 27
52.
c.3489+80C>T
rs2235048
Intron 27
53.
c.*193A>G
rs3842
3′ UTR
18
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