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

Polina Zalizko; Juris Stefanovics; Jelizaveta Sokolovska; Natalia Paramonova; Evija Klavina; Renars Erts; Vita Rovite; Janis Klovins; Aldis Pukitis

doi:10.1177/1756284820937426

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

Therap Adv Gastroenterol. 2020 Jul 14:13:1756284820937426. doi: 10.1177/1756284820937426. eCollection 2020.

Authors

Polina Zalizko¹, Juris Stefanovics², Jelizaveta Sokolovska³, Natalia Paramonova⁴, Evija Klavina², Renars Erts⁵, Vita Rovite⁶, Janis Klovins⁶, Aldis Pukitis²

Affiliations

¹ Faculty of Medicine, University of Latvia, Raina blv 19, Riga, 1586, Latvia.
² Pauls Stradins Clinical University Hospital, Riga, Latvia.
³ Faculty of Medicine, Laboratory of Personalized Medicine, University of Latvia, Riga, Latvia.
⁴ Genomics and Bioinformatics, Institute of Biology of the University of Latvia, Salaspils, Latvia.
⁵ Faculty of Medicine, University of Latvia, Riga, Latvia.
⁶ Latvian Biomedical Research and Study Centre, Riga, Latvia.

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.

Keywords: TPMT polymorphism; genotyping; inflammatory bowel disease; thiopurine; thiopurine S-methyltransferase.