ImmunosuppressionAgentThe 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
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Patients and Methods
We studied 133 Caucasian renal transplant recipients using 12-hour pharmacokinetic profiles including 15 transplant patients who showed the polymorphism and 15 transplant controls who were randomly chosen based on treatment with the same type and dosage of mycophenolate, same posttransplant time, and similar renal function. All patients who participated in the pharmacokinetic study were treated with tacrolimus.
Before blood sample collection, there had been no mycophenolate dose change for at
Results
The T-275A promoter mutation was detected in 12.03% of the 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) had more admissions due to gastrointestinal side effects (P < .05). The review of the patient medical histories showed a greater incidence and severity of gastrointestinal side effects in the patients with SNPs.
Pharmacokinetics studies showed that
Discussion
UGT1A9 is the key UGT responsible for glucuronidation of MPA to its inactive 7-O-glucuronide (MPAG). It is predominantly active in the liver, kidney, and intestine.13 We have evaluated the impact of specific SNPs of the UGT1A9 gene that resulted in increased in vitro glucuronidation activity (T-275A and C-2152T) and decreased enzymatic activity (UGT1A9⁎3 mutation).
The prevalences of T-275A and C-2152T SNPs of the UGT1A9 gene promoter region were similar to those previously described in the
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