Zalizko Polina, Stefanovics Juris, Sokolovska Jelizaveta, Paramonova Natalia, Klavina Evija, Erts Renars, Rovite Vita, Klovins Janis, Pukitis Aldis
Faculty of Medicine, University of Latvia, Raina blv 19, Riga, 1586, Latvia.
Pauls Stradins Clinical University Hospital, Riga, Latvia.
Therap Adv Gastroenterol. 2020 Jul 14;13:1756284820937426. doi: 10.1177/1756284820937426. eCollection 2020.
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 gene polymorphisms in a cohort of IBD patients in Latvia.
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 alleles (, and ) were identified (women, 51%; men, 49%). , and allelic variants detected using qPCR were consistent with restriction fragment length polymorphism (RFLP) data.
Among patients, 78% had ulcerative colitis and 22% had Crohn's disease, with 93.9% of the former carrying a wild-type homozygous genotype and 6.1% carrying heterozygous genotypes. The most frequent polymorphisms were (5.3%: two variants: and ), (0.4%), and (0.4%). None of the patients carried a polymorphism and no patients were homozygous for any mutation.
This is the first study to identify 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.
硫嘌呤甲基转移酶（TPMT）在硫嘌呤的代谢中起重要作用，对于炎症性肠病（IBD）患者，在使用硫唑嘌呤（AZA）治疗前进行TPMT基因分型很有用。在本研究中，我们测定了拉脱维亚一组IBD患者的基因多态性。
从244例IBD患者中获取DNA样本，并进行qPCR以检测rs1800462、rs1800460和rs1142345单核苷酸多态性（SNP）。鉴定出三个常见的无功能等位基因（、和）（女性占51%；男性占49%）。使用qPCR检测到的、和等位基因变体与限制性片段长度多态性（RFLP）数据一致。
在患者中，78%患有溃疡性结肠炎，22%患有克罗恩病，前者93.9%携带野生型纯合基因型，6.1%携带杂合基因型。最常见的多态性是（5.3%：两种变体：和）、（0.4%）和（0.4%）。没有患者携带多态性，也没有患者任何突变的纯合子。
这是第一项在拉脱维亚成年IBD患者中鉴定基因多态性的研究。结果表明，常见TPMT等位基因的频率与其他欧洲人群相似。
