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Association of CYP3A5 and POR polymorphisms with the maintenance tacrolimus dosage requirement in Thai recipients of kidney transplants

Kreetachon Veerakikosol
Kreetachon Veerakikosol
, 
Pajaree Chariyavilaskul
Pajaree Chariyavilaskul
, 
Natavudh Townamchai
Natavudh Townamchai
 e 
Supeecha Wittayalertpanya
Supeecha Wittayalertpanya
   | 31 mar 2017
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Article Category: Brief communication (Original)
Pubblicato online: 31 mar 2017
Pagine: 483 - 490
DOI: https://doi.org/10.5372/1905-7415.1005.512
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© 2016 Kreetachon Veerakikosol, Pajaree Chariyavilaskul, Natavudh Townamchai, Supeecha Wittayalertpanya
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Figure 1

Scatter dot plots of tacrolimus requirement doses, defined by 9 matching group genotypes. The groups are 1. CYP3A5*1/*1-POR*1/*1; 2. CYP3A5*1/*1-POR*1/*28; 3. CYP3A5*1/*1-POR*28/*28; 4. CYP3A5*1/*3-POR*1/*1; 5. CYP3A5*1/*3-POR*1/*28; 6. CYP3A5*1/*3-POR*28/*28; 7. CYP3A5*3/*3- POR*1/*1; 8. CYP3A5*3/*3-POR*1/*28, and 9. CYP3A5*3/*3-POR*28/*28.
Scatter dot plots of tacrolimus requirement doses, defined by 9 matching group genotypes. The groups are 1. CYP3A5*1/*1-POR*1/*1; 2. CYP3A5*1/*1-POR*1/*28; 3. CYP3A5*1/*1-POR*28/*28; 4. CYP3A5*1/*3-POR*1/*1; 5. CYP3A5*1/*3-POR*1/*28; 6. CYP3A5*1/*3-POR*28/*28; 7. CYP3A5*3/*3- POR*1/*1; 8. CYP3A5*3/*3-POR*1/*28, and 9. CYP3A5*3/*3-POR*28/*28.

Figure 2

Bar charts of mean ± standard error of tacrolimus dose requirements and P, defined by 9 matching group genotypes. *P < 0.05.
Bar charts of mean ± standard error of tacrolimus dose requirements and P, defined by 9 matching group genotypes. *P < 0.05.

Frequency of genotype distribution and mean dosage requirements of tacrolimus defined by 9 matching groups of genotypes.

Group123456789Total
GenotypeCYP3A5*1/*1-CYP3A5*1/*1-CYP3A5*1/*1-CYP3A5*1/*3-CYP3A5*1/*3-CYP3A5*1/*3-CYP3A5*3/*3-CYP3A5*3/*3-CYP3A5*3/*3-
POR*1/*1POR*1/*28POR*28/*28POR*1/*1POR*1/*28POR*28/*28POR*1/*1POR*1/*28POR*28/*28
N611121366213012150
%47.30.71824414208100
Mean dose (mg/kg/day)0.1630.1670.1410.1280.1310.1740.0810.0730.0690.113
SD0.0500.065–0.0570.0490.0650.0510.0310.0230.059

Baseline characteristics of 150 Thai recipients of kidney transplants, defined by CYP3A5 and POR genotype

ParametersCYP3A5 (n = 150)POR (n = 150)Total

P=0.013

1 expressers

P=0.013

3

P=0.013

1

P=0.013

28 mutation
Genotype

P=0.013

1/

P=0.013

1

P=0.013

1/

P=0.013

3

P=0.013

3/

P=0.013

3

P=0.013

11/

P=0.013

P=0.013

1/

P=0.013

28

P=0.013

28/

P=0.013

28		N/A
n(%)18(12)69(46)63 (42)54(36)77(51.3)19(12.7)150(100)
Male/female (n)11/731/3835/2824/3046/317/1277/73
Age (years)43.342.945.243.944.541.343.9
Weight (kg)59.756.059.058.457.855.457.7
Living donors (n)1130342837107575
Cadaveric donors (n)7392926409
Blood urea nitrogen (mg/dL)16.4(7.87)20.2(12.9)19.9(9.21)20.3(14.1)19.1(8.16)19.6(11.2)19.6(11.0)
Serum creatinine (mg/dL)1.38(0.47)1.37(0.40)1.48(0.72)1.33(0.41)1.48(0.65)1.41 (0.57)1.42(0.56)
Tacrolimus C0 (ng/mL)

P=0.013

6.53 (2.59)

P = 0.008 compared with CYP3A5*3/*3. Values are presented as mean (SD). C0: trough concentration.

7.15(2.52)		8.53 (2.79)7.68(2.77)7.71 (2.67)7.34(2.62)7.65 (2.69)
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