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Thiopurine Methyltransferase Genetic Polymorphisms and Activity and Metabolic Products of Azathioprine in Patients with Inflammatory Bowel Disease

[ Vol. 19 , Issue. 4 ]

Author(s):

Paria Pashazadeh, Abdoljalal Marjani*, Jahanbakhash Asadi and Masoud Khoshnia   Pages 541 - 547 ( 7 )

Abstract:


Background: Thiopurine S-methyltransferase (TPMT) is a cytoplasmic enzyme that catalyzes thiopurine drugs such as 6-mercaptopurine, 6-thioguanine, and azathioprine. There is a correlation between thiopurine drug metabolism, response, and toxicity and genetic polymorphism of TPMT. The aim of this study is to assess TPMT genetic polymorphisms activity and metabolic products of AZA in patients with IBD.

Methods: Blood samples were obtained from 50 IBD unrelated patients from a private laboratory. We used polymerase chain reaction-restriction length polymorphism (PCR-RFLP) and allele-specific PCRbased assays to determine the TPMT gene for the different variants. A high-performance liquid chromatography system (HPLC) was carried out to determine the whole blood 6-TGN concentration. Determination of serum TMPT activity was done by ELISA kit.

Results: In IBD patients, 46/50 (92%) subjects were homozygous for the wild-type allele (TPMT*1/*1). Mutant TPMT*1/*2 and TPMT*1/*3C alleles were found in 4/46 (8%) and 3/47 (6%) of IBD patients, respectively. TPMT*1/*3B variant was not detected in any of the IBD patients. TPMT enzyme activity was higher in wild-type than that mutant variants TPMT*1/*2 and TPMT*1/*3C, suggesting that there are statistically significant differences between 6-TG levels and polymorphisms of TMPT enzyme. 6-TG levels significantly increased in IBD patients mutant variants TPMT*1/*2 and TPMT*1/*3C.

Conclusions: Our results showed that TPMT polymorphisms are associated with 6-TGN levels in patients using AZA. This study suggests that AZA dosage may be determined according to the high or low prevalence of a TPMT genotype. Moreover, the results present the determination of metabolite for assessing possible safe effective dosage of the drug.

Keywords:

TPMT, gene, azathioprine, polymorphisms, IBD, Crohn’s disease, ulcerative colitis.

Affiliation:

Metabolic Disorders Research Center, Department of Biochemistry and Biophysics, , Gorgan Faulty of Medicine, Golestan University of Medical Sciences, Gorgan, Golestan Province, Metabolic Disorders Research Center, Department of Biochemistry and Biophysics, , Gorgan Faulty of Medicine, Golestan University of Medical Sciences, Gorgan, Golestan Province, Metabolic Disorders Research Center, Department of Biochemistry and Biophysics, , Gorgan Faulty of Medicine, Golestan University of Medical Sciences, Gorgan, Golestan Province, Golestan Research Center of Gasteroenterolgy and Hepatology, Golestan University of Medical Sciences, Gorgan, Golestan Province



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