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.
T., L., E., S., M., L., I., N., L., G., L., A., … F., L. (2012). High prevalence of polymorphism and low activity of thiopurine methyltransferase in patients with inflammatory bowel disease. European Journal of Internal Medicine, 23(3 PG-273–7), 273–277. https://doi.org/10.1016/j.ejim.2011.12.002