The prevalence of uridine diphosphate-glucuronosyltransferase 1A9 (UGT1A9) gene promoter region single-nucleotide polymorphisms T-275A and C-2152T and its influence on mycophenolic acid pharmacokinetics in stable renal transplant patients.
The aim of this study was to evaluate the distribution of UGT1A9 promoter region T-275A and C-2152T single nucleotide polymorphisms (SNPs) in stable transplant patients and to investigate the impact of these SNPs on mycophenolic acid (MPA) pharmacokinetics.


METHODS
In total, 133 Caucasian renal transplant recipients were studied. Also a complete 12-hour pharmacokinetic profile was recorded for 15 transplant patients who had the polymorphism and for 15 controls who were randomly chosen since they received the same type and dosage of mycophenolate, same posttransplant time and similar renal function.


RESULTS
The T-275A promoter mutation was detected in 12.03% of patients and the C-2152T in 9.77%. All patients with the mutation C-2152T had associated the mutation T-275A. Patients who carried either the T-275A or the C-2152T polymorphism (or both) experienced more admissions owing to gastrointestinal side effects (P < .05). The pharmacokinetics studies showed that carriers of T-275A and/or C-2152T displayed a smaller area under-concentration time curve (AUC): 57.8 +/- 4.3 vs 78.9 +/- 10.8 mg/L*h (P < .03).


CONCLUSIONS
It seemed that carriers of T-275A and C-2152T SNPs of the UGT1A9 gene promoter region in the late posttransplant recipient group, showed a greater incidence of gastrointestinal side effects and a lower MPA exposure.
Sánchez-Fructuoso
A I
AI
Nephrology Department, Hospital Clinico San Carlos, Madrid, Spain. sanchezfruct@telefonica.net
Maestro
M L
ML
Calvo
N
N
Viudarreta
M
M
Pérez-Flores
I
I
Veganzone
S
S
De la Orden
V
V
Ortega
D
D
Arroyo
M
M
Barrientos
A
A
D000225:Adenine; D000328:Adult; D003596:Cytosine; D004247:DNA / Q000097:blood / Q000235:genetics; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000453:epidemiology; D006580:Genetic Carrier Screening; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000502:physiology*; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000493:pharmacokinetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011401:Promoter Regions, Genetic; D016559:Tacrolimus / Q000627:therapeutic use; D013941:Thymine; D000090264:UDP-Glucuronosyltransferase 1A9; D044465:White People / Q000235:genetics
D007166:Immunosuppressive Agents; C000715591:UGT1A9 protein, human; D003596:Cytosine; D004247:DNA; D014453:Glucuronosyltransferase; D000090264:UDP-Glucuronosyltransferase 1A9; D009173:Mycophenolic Acid; D000225:Adenine; D013941:Thymine; D016559:Tacrolimus