Desatova B, Hlavaty T, Balakova D, Pav I, Celec P, Gregus M, Zakuciova M, Hlista M, Horakova M, Kadasi L, Huorka M, Batovsky M
Department of Internal Medicine V, Division of Gastroenterology and Hepatology, University Hospital Bratislava Ruzinov, Slovakia.
Bratisl Lek Listy. 2013;114(6):330-2. doi: 10.4149/bll_2013_069.
Thiopurine S-methyltransferase (TPMT) plays an important role in the metabolism of thiopurines. It has been suggested that TPMT genetic polymorphisms lead to dose-related hematopoietic toxicity. Since there are major ethnic differences in the prevalence of particular TPMT variants, it is important for each country to study their own prevalence in order to estimate the role of TPMT variants-related thiopurines toxicity in population suffering from particular inflammatory bowel disease (IBD).
The aim of this study was to determine the frequency of the four most common allelic variants of TPMT gene in the population of Slovak IBD patients.
TPMT genetic polymorphisms (TPMT2, TPMT3A, TPMT3B, TPMT3C) were amplified using PCR and consequently genotyped with genetic analyzer. The allele frequencies of particular allelic variants were calculated and compared with other Caucasian populations reported so far.
Three hundred and thirty IBD patients were included; 196/132/2 cases of Crohn´s disease/ulcerative colitis/unclassified colitis; 180 (55 %) males. Ninety-three percent of patients were homozygous for wild-type TPMT variant. Heterozygous genotype of any of the studied polymorphisms was present in 6 % of patients while only one patient was homozygous for TPMT3A allele (0.3 %). The most prevalent mutant allele was that of TPMT3A (3.2 %). The distribution of most common allelic variants of TPMT gene among Slovak IBD patients was in accordance with previously reported prevalence in Caucasian populations.
This study shows the prevalence of TPMT genetic polymorphisms in population of Slovak IBD patients. As in other Caucasian populations, the most common mutant allelic variant is that of TPMT*3A while the prevalence of homozygosity is relatively low (Tab. 3, Ref. 22).
硫嘌呤甲基转移酶（TPMT）在硫嘌呤的代谢中起重要作用。有研究表明，TPMT基因多态性会导致剂量相关的造血毒性。由于特定TPMT变体的患病率存在主要种族差异，每个国家研究自身的患病率对于评估TPMT变体相关的硫嘌呤毒性在特定炎症性肠病（IBD）患者群体中的作用很重要。
本研究的目的是确定斯洛伐克IBD患者群体中TPMT基因四种最常见等位基因变体的频率。
使用PCR扩增TPMT基因多态性（TPMT2、TPMT3A、TPMT3B、TPMT3C），随后用基因分析仪进行基因分型。计算特定等位基因变体的等位基因频率，并与迄今报道的其他白种人群体进行比较。
纳入330例IBD患者；其中克罗恩病/溃疡性结肠炎/未分类结肠炎患者分别为196/132/2例；男性180例（55%）。93%的患者为野生型TPMT变体纯合子。任何研究的多态性杂合基因型在6%的患者中存在，而只有1例患者为TPMT3A等位基因纯合子（0.3%）。最常见的突变等位基因为TPMT3A（3.2%）。TPMT基因最常见等位基因变体在斯洛伐克IBD患者中的分布与先前报道的白种人群体患病率一致。
本研究显示了斯洛伐克IBD患者群体中TPMT基因多态性的患病率。与其他白种人群体一样，最常见的突变等位基因变体是TPMT*3A，而纯合子的患病率相对较低（表3，参考文献22）。
