Department of Health Science, University of Catanzaro "Magna Graecia", Catanzaro, Italy.
Eur J Intern Med. 2012 Apr;23(3):273-7. doi: 10.1016/j.ejim.2011.12.002. Epub 2012 Jan 5.
Gene polymorphism of thiopurine methyltransferase (TPMT) correlates with decreased enzyme activity which determines a significant risk of adverse effect reactions (ADR) in patients treated with thiopurines. The aim of this study was to investigate TPMT genotype and phenotype status in patients with inflammatory bowel diseases (IBD).
Fifty-one consecutive out-patients with IBD were genotyped for the following allelic variants: rs1800462 (referred as TPMT 2 allele), rs1800460 (referred as TPMT 3B allele), and 1142345 (referred as TPMT 3C allele). Red blood cell TPMT activity was measured using a competitive micro-well immunoassay for the semi-quantitative determination of TPMT activity in red blood cells (RBC) by means of a 6-MP substrate.
Polymorphism of TPMT was found in 5 out of 51 patients (10%; 95% CI 2%-18%), three heterozygous and two homozygous carriers. Six patients (11.8%; 95% CI 2.4%-19.5%) displayed very low, 12 (23.5%; 95% CI 11.4%-34.5%) intermediate, and 33 (64.7%; 95% CI 52%-78%) normal/high TPMT activity. There were no differences between TPMT genotype and phenotype groups according to age, type of disease, smoking, and chronic medications. A 71% (95% CI 61%-81%; κ=0.45) concordance rate was found between genotype and phenotype status. Six out of 27 (22%) current or past users of azathioprine developed ADR, with three (50%) displaying TPMT genotype and/or phenotype alterations.
Compared to the general population, IBD patients may have significantly higher prevalence of TPMT polymorphism and, even more, low activity. Phenotypic more than genotypic TPMT analysis could be useful to better manage IBD therapy with thiopurines.
巯基嘌呤甲基转移酶（TPMT）基因多态性与酶活性降低相关，而酶活性决定了接受巯嘌呤治疗的患者发生不良反应（ADR）的显著风险。本研究旨在探讨炎症性肠病（IBD）患者的 TPMT 基因型和表型状态。
对 51 例连续就诊的 IBD 患者进行以下等位基因变异的基因分型：rs1800462（称为 TPMT 2 等位基因）、rs1800460（称为 TPMT 3B 等位基因）和 1142345（称为 TPMT 3C 等位基因）。使用竞争性微孔免疫测定法检测红细胞 TPMT 活性，以半定量测定红细胞（RBC）中 TPMT 活性，使用 6-MP 作为底物。
在 51 例患者中有 5 例（10%；95%CI 2%-18%）发现 TPMT 多态性，其中 3 例为杂合子携带者，2 例为纯合子携带者。6 例（11.8%；95%CI 2.4%-19.5%）显示极低、12 例（23.5%；95%CI 11.4%-34.5%）中间和 33 例（64.7%；95%CI 52%-78%）正常/高 TPMT 活性。根据年龄、疾病类型、吸烟和慢性药物治疗，TPMT 基因型和表型组之间没有差异。基因型和表型状态之间的一致性率为 71%（95%CI 61%-81%；κ=0.45）。27 例当前或既往使用硫唑嘌呤的患者中有 6 例（22%）发生 ADR，其中 3 例（50%）显示 TPMT 基因型和/或表型改变。
与一般人群相比，IBD 患者的 TPMT 多态性发生率可能显著更高，而且活性降低的情况更为常见。表型 TPMT 分析比基因型 TPMT 分析更有助于更好地管理 IBD 患者的巯嘌呤治疗。
