2.12 OATP1B1*1a OATP1B1*2 OATP1B1*3
OATP1B1*5 OATP1B1*6 OATP1B1*9 OATP1B1*12 OATP1B1
rifampin Tirona et al. 2002 OATP1B1*15
OATP1B1*1b pravastatin OATP1B1*1a Estradiol 17 -D-glucuronide ( E2G)
rifampin OATP1B1
(subatrate-dependent genetic variation
82 OATP1B1*5(T521C)
OATP1B1 OATP1B1 Gilbert’s syndrome
Gilbert’s syndrome bilirubin AST/ALT
rifampin hyperbilirubinemia Gilbert’s syndrome Gilbert’s syndrome rifampin
hyperbilirubinemia OATP1B1
83, 84
OATP1B1 OATP1B1
hyperbilirubinemia rifampin OATP1B1 rifampin
bilirubin AST/ALT Gilbert’s syndrome
1965 rifampin
OATP1B1 Bromosulfophthalein( BSP) BSP bilirubin
1~2 rifampin bilirubin
rifampin hyperbilirubinemia isoniazid
isoniazid 85
(1) OATP1B1 rifampin
isoniazid
(2) OATP1B1 rifampin
bilirubin
isoniazid rifampin OATP1B1
OATP1B1 rifampin rifampin
isoniazid OATP1B1
bilirubin bilirubin
3
3.1
(retrospective study) 94 12 1 96
4 30
CIMOS case control
DNA PCR-RFLP OATP1B1
OATP1B1 3.1
(94/12/1~96/4/30)
DNA PCR-RFLP OATP1B1
CIMOS
case control
3.2
3.2.1
(1) 94 12 1 96 4 30
(2)
(3) ( 1)
(4) Rifampicin® (Rifampin 150
mg/capsule) INAH® (Isoniazid 100 mg/tablet) Myambutol® (Ethambutol 400 mg/tablet) Pyramide® (Pyrazinamide 250 mg/tablet) Mide®
(Pyrazinamide 500 mg/tablet) Rifater® (Rifampin 120 mg, isoniazid 80 mg, pyrazinamide 250 mg) Rifinah 150® (Rifampin 150 mg, isoniazid 100 mg) Rifinah 300® (Rifampin 300 mg, isoniazid 150 mg)
3.2.2
(1) ALT AST Tbil
(2) hepatitis B surface antigen
(HBsAg) hepatitis C virus (HCV) antibody hepatitis A virus (HAV) immunoglobulin M antibody
3.3
( 2)
(1)
( ) ( )
(2)
(3) albumin aspartate aminotrasnferase (AST) alanine aminotransferase (ALT) total bilirubin (Tbil) direct bilirubin (Dbil) serum alkaline phosphate (ALP) hepatitis C virus (HCV) antibody hepatitis B surface antigen (HBsAg) human immunodeficiency virus (HIV) antibody blood urea nitrogen (BUN) serum creatinine (SCr)
(Day 1) 3.1
Day 1 Day 3
Day 5 Day 7
3.4
3.4.1
(The Council for International Organizations of Medical Sciences CIOMS) ( 3.2)
Day 0 (D0) -28
Baseline
Day 1 (D1)
1 0
Day 3 (D3) 3 2-4 1
Day 5 (D5) 5 4-6 1
Week 1 (W1) 7 6-8 1
Week 2 (W2) 14 11-17 3
Week 3 (W3) 21 18-24 3
Month 1 (M1) 28 25-31 3
Week 5 (W5) 35 32-38 3
Week 6 (W6) 42 39-45 3
Week 7 (W7) 49 46-52 3
Month 2 (M2) 56 53-59 -3~+14
Month 3 (M3) 84 70-98 14
Month 4 (M4) 112 98-126 14
Month 5 (M5) 140 126-154 14
Month 6 (M6) 168 154-182 14
3.1
3.2 CIOMS
1. ALT AST ALP Tbil N~2N
2. AST ALP Tbil >2N
1. ALT >2N
2. Direct bilirubin (Dbil) >2N
3. AST ALP Tbil >2N
1. ALT >2 N 2. R 5
1. ALP >2N 2. R 2
1. ALT >2N ALP >2 N 2. 2<R<5
R=ALP ULN ULN
ALT (ULN= )
3.3
AST 5-30 U/L
ALT 5-35 U/L
Total bilirubin (Tbil) 0-1.2 mg/dl Direct bilirubin (Dbil) 0-0.4 mg/dl
3.4.2
Naranjo Score RUCAM Score ( 3 4)
Naranjo Score 10
(double) ( 0
) (possible) (1-4 ) (probable) (5-8 ) (definite)
(9 )
The Roussel Uclaf Causality Assessment Method (RUCAM)
The Council for International Organization of Medical Science, CIOMS RUCAM Score
(hepatocellular type) (Cholestastic or Mixed type)
( )
excluded 0
unlikely 1-2 possible 3-5 probable
6-8 highly probable >8
3.4.3
1. CIOMS
( )
2.
3.
3.5
DNA
(polymerase chain reactions PCR) DNA PCR
(restriction fragment lenth polymorphism RFLP)
SNP 3.2
OATP1B1*1b OATP1B1*5 allele Restriction Enzyme
3.2 DNA 3 primer ( 3.4) PCR 4S+4AS
PCR TaqI RFLP OATP1B1*1b 5F+5R PCR
HhaI RFLP OATP1B1*5 5F+5-2R PCR
DNA OATP1B1*5 positive control
OATP1B1*1b OATP1B1*5 SNP allele
( OATP1B1*15 4F+5R long-range PCR SNP
ClaI+HhaI RFLP OATP1B1*15
allele OATP1B1*1b OATP1B1*5 PCR RFLP
3.5.2 3.3
primer SNP
3.4 OATP1B1 Primer
Primer name Sequence
4S 5’-ATT CAG TGA TGT TCT TA-3’
4AS 5’-CTG TCA ATA TTA ATT CTT-3’
4F 5’-AGA GTC ATA CAT TAG AGC GT-3’
5F 5’-CAA GTA GTT AAA TTT GTA AT -3’
5R 5’-GAA GCA TAT TAC CCA TGA GC-3’
5-2R 5’-GAA GCA TAT TAC CCA TGA GCG CAT ATA
TCC
*“_” mutagenesis site
4F (20 bp) 4S (17 bp) 4AS (18 bp)
3.5.1 DNA
DNA 5 c.c. EDTA
50 mL NH4Cl (J.T.Baker, 0660-01) 50mL
4 1250~1500 r.p.m. 10
15mL (phosphoryl buffer solution, PBS, 90 g NaCl (J.T Baker, 3624-01)+2.1 g KH2PO4 (J.T Baker, 3246-01)+3.84 g Na2HPO4 (J.T Baker,
3828-01) ddH2O 1000 mL 100 mL 900 mL ddH2O 1
PBS) 1500 r.p.m. 5 500 L protein lysis buffer
(0.1M Tris-HCl (AMRESCO, 0826-1)+0.1M NaCl+2mM EDTA (AMRESCO,0105-1)) 3 L 20 mg/mL proteinase K (AMRESCO, 0706-100) 37 incubator phenol-chloroform (SIGMA,
P3803-400) 4 14000 r.p.m. 10
chloroform (CKANTO CHEMICAL, 07278-00) 4 14000 r.p.m.
10 isopropenol (J.T Baker, 9084-03) 1/10
3.0M (SIGMA, S-1804) -80 3 ( )
4 14000 r.p.m. 15 1 mL 75 ethanol (J.T
Baker, 8006-05) 30~50 L TE buffer (AMRESCO, 0100-1)
DNA -80
3.5.2
(polymerase chain reactions PCR) DNA
PCR (restriction fragment lenth
polymorphism RFLP) SNP
OATP1B1*1b (A388G) OATP1B1*5 (T521C) OATP1B1*15 (A388G + T521C) OATP1B1*5 (restriction enzyme cutting site) mutagenesis
PCR primer DNA PCR
RFLP TaqI HhaI ClaI
TaqI 5’-T^CGA-3’ HhaI 5’-GCG^C-3’ ClaI
5’-AT^CGAT-3’ SNP DNA (
wild type) SNP
OATP1B1*5 (T521C) SNP
positive control SNP
OATP1B1*5 primer mutagenesis PCR OATP1B1*5
DNA TA (ligation) (competent cell)
DNA PCR PCR
product positive control
OATP1B1*1b (A
388G) PCR-RFLP
2 L DNA 2 L 2.5 mM dNTP (Protech, PT-8014) 2 L 5 M Primer [4S+4AS] (Protech, P52956 P52957) 2.5 L 10X Taq buffer [Mg2+ free] (Protech, PROTAQ-B) 1.75 L 25mM MgCl2 (Protech, PT-PROTAQ-B-1) 0.5 L 2U Pro Taq Plus DNA Polymerase (Protech, PMT526) 14.25 L ddH2O 25 L
Thermocycler (Astec PC806) PCR 94 30 52
30 72 1 cycle annealing 1 6
cycle (annealing 52 46 ) 7~40 cycle 94 30
46 30 72 1 72 10 cool down
4
PCR 10 L PCR product (162 bp) 0.5 L
10U/ L TaqI (Promega, R615A) 5 L Mineral oil (Protech, MINERALOIL) 56 2.5
OATP1B1*5 (T
521C) PCR-RFLP
2 L DNA 2 L 2.5 mM dNTP (Protech, PT-8014) 2 L 5 M Primer [5F+5R] (Protech, P61371 P61372) 2.5 L 10X Taq buffer (Protech, PT-525-B) 0.5 L 2U Pro Taq Plus DNA Polymerase (Protech, PMT526) 16 L ddH2O 25 L
Thermocycler (Astec PC806) PCR 94 1 50
30 72 30 40 cycles 72 10
cool down 4
PCR 10 L PCR product (130 bp) 0.5 L
10U/ L HhaI (Promega, R644A) 37 3
OATP1B1*15 (A
388G +T
521C) PCR-RFLP
2 L DNA 2 L 2.5 mM dNTP (Protech, PT-8014) 2 L 5 M Primer [4F +5R] (Protech, P52956 P61372) 2.5 L 10X Taq buffer (Protech, PT-525-B) 0.5 L 2U Pro Taq Plus DNA Polymerase (Protech, PMT526) 16 L ddH2O 25 L
Thermocycler (Astec PC806) PCR 94 2 52
2 72 2 40 cycles 72 10
cool down 4
PCR 10 L PCR product (2280 bp) 0.5 L
10U/ L ClaI (BioLabs, R0197S) 0.5 L 10U/ L HhaI (Promega, R644A) 37 3
DNA (plasmid DNA)
DNA OATP1B1*5
RFLP OATP1B1*5
PCR PCR SNP
DNA (positive
control) DNA
1. PCR (Mutagenesis)
2 L DNA 2 L 2.5 mM dNTP (Protech, PT-8014) 2 L 5 M Primer [5F+5R-2] (Protech, P61371 P61373) 2.5 L 10X Taq buffer (Protech, PT-525-B) 0.5 L 2U Pro Taq Plus DNA Polymerase (Protech, PMT526)
2. (Ligation)
5 L mutangenesis PCR product (209 bp) yT&A
(Yeastern Biotech, YC001) 2 L yT&A vector (25ng/ L) 1 L Ligation buffer A (10X) 1 L Ligation buffer B (10X) 1 L YEA T4 DNA ligase (2U/ L) 20 6
3. (Transformation)
42 4 ECOS (Yeastern
Biotech, YE707) 20 30
1/3 2.5 L 50 L ECOS
vortex 1 42 45
( vortex 1 ) 4 (
100mM IPTG 1.6 L 50 mg/mL X-gal 50 L Luria-Bertani (BIOBASIC, S518)-ampicillin ( , 032E52A)) 37 overnight
4. (Blue and White Screening)
yT&A vector ampicillin yT&A
vector E. Coli LB-ampicillin yT&A vector
E. Coli LacZ( -galactosidase) LacZ X-gal
DNA yT&A vector MCS
(multiple cloning site) LacZ E. Coli
LacZ yT&A vector MC E.
Coli LacZ X-gal IPTG
LacZ yellow tip
5 mL 1X ampicillin LB 37
5. DNA(Plasmid DNA )
Protech techbology Gene-SpinTMMiniPrep Kit (Protech, MP530XL)
DNA 1.5 ml 13000 r.p.m.
1 1.5 ml
200 l solution I 200 l solution II
5 ~ 6 200 lsolution III
13000 rpm
5 kit spin column collection tube
spin column 30 spin column
collection tube spin column 700 l washing
solution 30 collection tube 3
spin column 50 l elution buffer
3.5.3
TaqI HhaI 8% polyacrylamide gel (7.89 mL 0.5X TAE
buffer (AMRESCO, K915-1) + 2 mL ACRYL/BIS 19:1 solution (AMRESCO, 0496-500) + 100 L 10% Ammonium Persulfate (AMRESCO, 0486-25) + 10 L TEMED
(AMRESCO, 0761-25)) 100 55 100 ClaI HhaI
1% agarose gel (0.4g Agarose 3:1 HRBTM(Protech, E776) +
40 mL 0.5X TAE buffer) 100 40 SYBRR Green I
Nucleic Acid Gel Stain (Sigama-Aldrich, 86205) 30 UV 3.4 3.6
3. OATP1B1*1b 200
300
150
100
50
*1a/*1a *1a/*1b *1b/*1b
92 bp 70 bp
47 bp
23 bp
3.5 OATP1B1*5
*1a/*15 Uncut 250
300
200
150
100
*1a/*1a *1a/*5 *5/*5
130 bp 111 bp
2500
1000
500 1500 2000 3000
2280 bp 1814 bp
3.5.4 OATP1B1
OATP1B1
1. OATP1B1 (allele)
(1) OATP1B1*1a OATP1B1
(2) OATP1B1*1b OATP1B1 genomic DNA 388
adenine (A) guanine (G)
(3) OATP1B1*5 OATP1B1 genomic DNA 521
thymine (T) guanine (C)
(4) OATP1B1*15 OATP1B1*1b OATP1B1*5
2. OATP1B1 (genotype) OATP1B1
(1) OATP1B1 OATP1B1
OATP1B1*1a/*1a
(2) OATP1B1 OATP1B1
OATP1B1*1b OATP1B1*5 OATP1B1*15
3. (allele frequency)
4. OATP1B1*5 OATP1B1*5 OATP1B1*15
5. (homozygous genotype) (allele)
3.6
Excel SPSS 13.0 for Windows (continuous and categorical data)
OATP1B1 Pearson Chi-square test
5 Fisher’s exact test OATP1B1
Odds Ratio 95% (confidence interval) (Body mass index BMI)
independent t-test nonparametric
Wilcoxon rank sum test Naranjo Score RUCAM Spearman’s Rho test P<0.05
4
4.1
4.1.1
94 12 1 96 4 30
102 97
5 2 B 3 C
4.1.2
4.1 97 65 (67% 32
(33%) 2 54.8
24 (24.7%) 30 (30.9%) 8
(8.2%) 5 (5.2%) 4 (4.1%)
(42 43.3%)
(24 24.7%) 21 (21.6%) 4 (4.1%)
4 (4.1%)
HERZ
HER 6 6.2%
4.1 (97 )
(Diabetes mellitus) 30(30.9)
(Asthma) 3(3.1)
(COPD) 5(5.2)
(GI-related disease) 8(8.2)
(Renal disease) 3(3.1)
(Liver disease) 4(4.1)
42(43.3)
Rifampin (RIF) mg/kg 10.3±1.7
4.1.3
AST ALT 76 (78.4%)
73 (75.3%) Total bilirubin direct bilirubin ALP
29 (29.9% 10 (10.3%) 6 (6.2%) ( 4.2 4.1)
( ) ( )
AST 76(78.4%) 5-30 U/L 22(9~56)
ALT 73(75.3%) 5-35 U/L 17(7~53)
Total bilirubin 29(29.9%) 0-1.2 mg/dl 0.59(0.23~1.97) Direct bilirubin 10(10.3%) 0-0.4 mg/dl 0.20(0.01~0.04)
ALP 6(6.2%) 50-136 U/L 69(41~138)
%
4.2
4.2
4.2.1
59 (60.8%)
43 (44.3%) 16 (16.5%)
12 (12.3%) 1
(1.0%) 3 (3.2%) 4.2
4.2
4.2.2
CIOMS (
)
12 (12.3%)
16 (16.5%)
38 (39.2%) 43 (44.3%)
1 (1.0%)
3 (3.2%)
Naranjo Score
16 6 (37.5%)
(possible) 6 (37.5%) (probable)
4 (25%) (
(definite)
RUCAM
3 (18.75%) (possible) 7 (43.75%) (probable)
6 (highly probable)
( 4.4) Naranjo Score RUCAM 0.826
(P<0.01)
4.3 Naranjo Score
4.3
4.3.1
( )
16 81
4.5
BMI (
rifampin isoniazid pyrazinamide ethambutol
( 50.7±10.8 kg 56.8±10.2
kg) ethambutol 800mg/qd
ethambutol
4.5
(%) 10(62.5) 55(67.9)
(%) 6(37.5) 26(32.1)
62.4±20.3 53.2±20.5 0.104
(cm) 160.5±10.5 163.8±7.9 0.187
(kg) 50.7±10.8 56.8±10.2 0.048*
(Body mass index, BMI) 19.3±2.8 21.3±3.5 0.055
5(31.25) 19(23.5) 0.354
4(25) 26(32.1) 0.405
1(6.25) 2(2.5) 0.421
5(6.2) 0.398
2(12.5) 6(7.4) 0.392
2(12.5) 1(1.2) 0.07
1(6.25) 4(4.9) 0.602
4(25) 38(46.9) 0.088
2(12.5) 22(27.1) 0.179
6(37.5) 15(18.5) 0.092
4(4.9) 0.48
1(6.25) 3(3.7) 0.52
Rifampin (RIF) mg/kg 10.55±2.58 10.24±1.47 0.175
Isoniazid (INH) mg/kg 6.8±1.16 6.52±1.55 0.505
Pyrazinamide (PZA) mg/kg 17.8±10.03 19.07±7.54 0.755 Ethambutol (EMB) mg/kg 14.87±5.23 11.86±5.43 0.022*
4.3.2
4.6
AST ALT Tbil
AST ALT 10
Tbil (1.2mg/dL) CIOMS
4.6
P value
(N=16) (N=81)
( ) ( )
AST(U/L) 30(13-56) 22(9-52) 0.812
ALT(U/L) 21 (9-42) 16(7-53) 0.271
Total bilirubin(mg/dL) 0.63(0.23-1.1) 0.59(0.24-1.97) 0.82
AST (U/L) 157(37-1680) 29.5(6-159) <0.001
ALT (U/L) 143(54-2285) 22(6-67) <0.001
Total bilirubin
(mg/dL) 0.91(0.6-2.54) 0.76(0.28-2.68) 0.011
4.3.3 OATP1B1
OATP1B1*1a OATP1B1*1b OATP1B1*5 OATP1B1*15
OATP1B1 7 4.7 OATP1B1
OATP1B1
*1a/*5 *15/*15 OATP1B1*5( OATP1B1*5 OATP1B1*15)
OATP1B1*1a
OATP1B1*1a OATP1B1*1a
OATP1B1*1a
(Odds Ratio) 95% (Confidence Interval)
OR 95% CI P value (N=16) (N=81)
(%) (%)
OATP1B1 genotype
OATP1B1*1a/*1a 2(12.5) 4(4.9) 2.75 0.46-16.48 0.257 OATP1B1*1a/*1b 4(25) 26(32.1) 0.71 0.21-2.39 0.405 OATP1B1*1b/*1b 7(43.75) 34(42) 1.08 0.36-3.17 0.554
OATP1B1*1a/*5 1(1.2) 0.835
OATP1B1*1a/*15 2(12.5) 2(2.5) 5.64 0.73-43.43 0.126 OATP1B1*1b/15 1(6.25) 13(16.1) 0.35 0.04-2.88 0.28
OATP1B1*15/*15 1(1.2) 0.835
With *5 3(18.8) 17(21) 0.87 0.22-3.4 0.572
Number of OATP1B1*1a
Two OATP1B1*1a 2(12.5) 4(4.9) 2.75 0.46-16.48 0.257 One OATP1B1*1a 6(37.5) 29(35.8) 1.08 0.36-3.26 0.554
No OATP1B1*1a 8(50) 48(59.3) 0.69 0.24-2.01 0.339
4.7 OATP1B1
4.3.4 OATP1B1
OATP1B1
( 4.8) OATP1B1*5
OATP1B1*5 OATP1B1*15( OATP1B1*1b allele ) OR OATP1B1*1a OATP1B1*1b OATP1B1*15
OATP1B1*5 OR ( 4.12)
4.8 OATP1B1
OR 95% CI P value
(N=32) (N=162)
(%) (%)
OATP 1B1*1a 10(31.35) 37(22.8) 1.54 0.67-3.53 0.31 OATP 1B1*1b 19(59.4) 107(58.8) 0.75 0.35-1.63 0.47
OATP 1B1*5 1(0.5) 0.84
OATP 1B1*15 3(9.4) 17(9.3) 0.88 0.24-3.20 0.57
4.4 OATP1B1
OATP1B1
OATP1B1 6
(6.2% OATP1B1 91 (93.8%)
( 4.9)
OATP1B1 OATP1B1 P value
N=6 N=91
( ) ( )
AST (U/L) 20 (13~26) 29 (9~56) 0.631
ALT (U/L) 17 (11~22) 19 (7~53) 0.398
Total bilirubin (mg/dL) 1.97 ( ) 0.66 (0.23~1.96) *
AST (U/L) 100.8 (19-414) 85.8 (6-1680) 0.857
ALT (U/L) 116.5 (15-511) 86.2 (6-2285) 0.794
Total bilirubin
(mg/dL) 1.3 (0.53-2.68) 0.96 (0.28-2.54) 0.335
*OATP1B1 Total bilirubin P value
4.9 OATP1B1
OATP1B1*5
OATP1B1*5( OATP1B1*5 OATP1B1*15) OATP1B1*5
( 4.10)
OATP1B1*5 OATP1B1*5 P value
N=20 N=77
( ) ( )
AST (U/L) 30 (9~56) 24 (11~50) 0.364
ALT (U/L) 20.1 (7~53) 16.8 (11~29) 0.213
Total bilirubin (mg/dL) 0.69 (0.23~1.97) 0.81 (0.32~1.96) 0.133
AST (U/L) 67(6-557) 92.1(16-1680) 0.614
ALT (U/L) 105.7(6-1287) 83.4(6-2285) 0.748
Total bilirubin
(mg/dL) 1.01(0.42-2.54) 0.98(0.28-2.68) 0.841 4.10 OATP1B1*5
5
5.1
97 59 (60.8%) 16
(16.5%) 43 (44.3%)
( AST<30 U/L ALT<35 U/L )
( 54 86) ( 5.1)
5.1
*
(%)
Chen (2007) 97 Hepatotoxitity (CIOMS definition) 59 60.8
Chen (2007) 97 Liver Injury (CIOMS definition) 16 16.5
Kao (2006) 254 Hepatotoxitity (CIOMS definition) 126 49.61
Kao (2006) 254 Liver Injury (CIOMS definition) 52 20.47
Lo (1998) 348 Hepatotoxitity (CIOMS definition) 207 59.48
Lo (1998) 348 Liver Injury (CIOMS definition) 120 34.50
Chen (2002) 261 Hepatotoxitity (CIOMS definition) 152 58.24
Chen (2002) 261 Liver Injury (CIOMS definition) 83 31.80
Hsiao (2003) 245 Hepatotoxicity (CIOMS definition) 122 49.80
Hsiao (2003) 245 Liver Injury (CIOMS definition) 41 16.73
OATP1B1 allele frquency
OATP1B1
OATP1B1*1b OATP1B1*5 OATP1B1*15 OATP1B1*1a allele
OATP1B1*1b(64.9%) OATP1B1*1a (24.2%) wild type
OATP1B1 OATP1B1*1b OATP1B1*1a OATP1B1
wild type ( 5.2 5.3)
*1a 24.2% 22.22% 35.2%
80% 30% 75%
Chen (N=97) Lu (N=162) Japanese (N=267) OATP1B1 genotype
5.3 OATP1B1 allele frequency
OATP1B1 allele frequency
OATP1B1 allele frequency
1. OATP1B1
2. OATP1B1
3. OATP1B1
( )
( NAT2 CYP2E1 )
5.2
1.
16 OATP1B1
primary outcome =0.05
power=0.8 20%
38 190 allele
OATP1B1*5 primary outcome =0.05 power=0.8 20%
2797 13985 ( Power and Sample
Size Calculations Ver2.1.31 )
2.
Tbil Dbil ALP
3.
OATP1B1 rifampin
rifampin isoniazid pyrazinamide
4. OATP1B1 rifampin
OATP1B1 rifampin
(in vitro) (in vivo)
OATP1B1 rifampin
5. OATP1B1
OATP1B1*1a OATP1B1*1b OATP1B1*5 OATP1B1*15 OATP1B1
5
rifampin
OATP1B1
6
4
1. 16.5%
2. OATP1B1*1b(64.9%) OATP1B1*1a (24.2%) allele frequency
3. OATP1B1*1a/*5
4. OATP1B1*1b OATP1B1*5 OATP1B1*15
OATP1B1 4
1. . . : ; 2004.
2. Charles A. Peloquin. Chapter 110: Tuberculosis. In: Joseph T. Dipiro, Robert L.
Talbert, Gary C.Yee, Gary R. Matzke, Barbara G. Wells, L. Michael Posey, eds.
Pharmacotherapy: A pathopnysiologic approach 6ed: Mc Graw-Hill Publishing Co. ; 2005:2015-34.
3. 2006 Tuberculosis Facts. 2007. (Accessed March, 2007, at
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