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Thiopurine S-methyltransferase genetic polymorphisms in adult patients with inflammatory bowel diseases in the Latvian population.

ABSTRACT: Background:Thiopurine methyltransferase (TPMT) plays a significant role in the metabolism of thiopurines, and, for patients with inflammatory bowel disease (IBD), it is useful to perform TPMT genotyping prior to azathioprine (AZA) treatment. In this study, we determined TPMT gene polymorphisms in a cohort of IBD patients in Latvia. Methods:DNA samples were obtained from 244 IBD patients, and qPCR was performed for detection of rs1800462, rs1800460, and rs1142345 single-nucleotide polymorphisms (SNPs). Three common, non-functional TPMT alleles (TPMT*2, *3B, and *3C) were identified (women, 51%; men, 49%). TPMT*2, *3A, *3B, and *3C allelic variants detected using qPCR were consistent with restriction fragment length polymorphism (RFLP) data. Results:Among patients, 78% had ulcerative colitis and 22% had Crohn's disease, with 93.9% of the former carrying a wild-type homozygous TPMT*1/*1 genotype and 6.1% carrying heterozygous genotypes. The most frequent polymorphisms were TPMT*1/*3A (5.3%: two variants: TPMT*3B and TPMT*3C), TPMT*1/*3C (0.4%), and TPMT*1/*2 (0.4%). None of the patients carried a TPMT*3B polymorphism and no patients were homozygous for any mutation. Conclusion:This is the first study to identify TPMT gene polymorphisms in adult IBD patients in Latvia. The results indicate that the frequency of common TPMT alleles is similar to that of other European populations.

SUBMITTER: Zalizko P

PROVIDER: S-EPMC7361485 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Thiopurine <i>S</i>-methyltransferase genetic polymorphisms in adult patients with inflammatory bowel diseases in the Latvian population.

Zalizko Polina P Stefanovics Juris J Sokolovska Jelizaveta J Paramonova Natalia N Klavina Evija E Erts Renars R Rovite Vita V Klovins Janis J Pukitis Aldis A

Therapeutic advances in gastroenterology 20200714

<h4>Background</h4>Thiopurine methyltransferase (TPMT) plays a significant role in the metabolism of thiopurines, and, for patients with inflammatory bowel disease (IBD), it is useful to perform TPMT genotyping prior to azathioprine (AZA) treatment. In this study, we determined <i>TPMT</i> gene polymorphisms in a cohort of IBD patients in Latvia.<h4>Methods</h4>DNA samples were obtained from 244 IBD patients, and qPCR was performed for detection of rs1800462, rs1800460, and rs1142345 single-nucl ...[more]

PMID: 32704308

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Project description:PurposeThiopurine drugs are well established treatments in the management of inflammatory bowel disease (IBD), but their use is limited by significant adverse drug reactions (ADRs). Thiopurine S-methyltransferase (TPMT) is an important enzyme involved in thiopurine metabolism. Several clinical guidelines recommend determining TPMT genotype or phenotype before initiating thiopurine therapy. Although several studies have investigated the association between TPMT polymorphisms and thiopurine-induced ADRs, the results are inconsistent. The purpose of this study is to evaluate whether there is an association between TPMT polymorphisms and thiopurine-induced ADRs using meta-analysis.MethodsWe explored PubMed, Web of Science and Embase for articles on TPMT polymorphisms and thiopurine-induced ADRs. Studies that compared TPMT polymorphisms with-ADRs and without-ADRs in IBD patients were included. Relevant outcome data from all the included articles were extracted and the pooled odds ratio (OR) with corresponding 95% confidence intervals were calculated using Revman 5.3 software.ResultsFourteen published studies, with a total of 2,206 IBD patients, which investigated associations between TPMT polymorphisms and thiopurine-induced ADRs were included this meta-analysis. Our meta-analysis demonstrated that TPMT polymorphisms were significantly associated with thiopurine-induced overall ADRs and bone marrow toxicity; pooled ORs were 3.36 (95%CI: 1.82-6.19) and 6.67 (95%CI: 3.88-11.47), respectively. TPMT polymorphisms were not associated with the development of other ADRs including hepatotoxicity, pancreatitis, gastric intolerance, flu-like symptoms and skin reactions; the corresponding pooled ORs were 1.27 (95%CI: 0.60-2.71), 0.97 (95%CI: 0.38-2.48), 1.82 (95%CI: 0.93-3.53), 1.28 (95%CI: 0.47-3.46) and 2.32 (95%CI: 0.86-6.25), respectively.ConclusionsOur meta-analysis demonstrated an association of TPMT polymorphisms with overall thiopurine-induced ADRs and bone marrow toxicity, but not with hepatotoxicity, pancreatitis, flu-like symptoms, gastric intolerance and skin reactions. These findings suggest that pretesting the TPMT genotype could be helpful in clinical practice before initiating thiopurine therapy. However, white blood cell count analysis should be the mainstay for follow-up.

Dataset Information

Thiopurine S-methyltransferase genetic polymorphisms in adult patients with inflammatory bowel diseases in the Latvian population.

Publications

Thiopurine <i>S</i>-methyltransferase genetic polymorphisms in adult patients with inflammatory bowel diseases in the Latvian population.

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