Acta clinica Croatica, Vol. 55. No. 1., 2016.
Original scientific paper
https://doi.org/10.20471/acc.2016.55.01.3
An Epidemiological Study of Thiopurinemethyltransferase Variants in a Croatian Inflammatory Bowel Disease Patient Cohort
Agata Ladić
; Division of Gastroenterology and Hepatology, Zagreb Univesity Hospital Center, Zagreb, Croatia
Nada Božina
; Clinical Department of Laboratory Diagnosis, Zagreb University Hospital Center, Zagreb, Croatia ; School of Medicine, University of Zagreb, Zagreb, Croatia
Vladimir Borzan
; Division of Gastroenterology, Osijek University Hospital Center, Osijek, Croatia
Marko Brinar
; Division of Gastroenterology and Hepatology, Zagreb University Hospital Center, Zagreb, Croatia; School of Medicine, University of Zagreb, Zagreb, Croatia
Boris Vucelić
; Division of Gastroenterology and Hepatology, Zagreb University Hospital Center, Zagreb, Croatia; School of Medicine, University of Zagreb, Zagreb, Croatia
Silvija Čuković-Čavka
; Division of Gastroenterology and Hepatology, Zagreb University Hospital Center, Zagreb, Croatia; School of Medicine, University of Zagreb, Zagreb, Croatia
Abstract
Thiopurine S-methyltransferase (TPMT) is an enzyme that converts thiopurine drugs into inactive metabolites. Over 20 variant TPMT-encoding alleles, which cause reduced enzymatic activity, have been discovered so far. Our aim was to investigate the frequencies of variant alleles, i.e. genotypes in inflammatory bowel disease (IBD) patients and healthy individuals and to compare these frequencies with selected world populations. The most common variant alleles
TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C were analyzed with polymerase chain reactionbased assays and allele-specific polymerase chain reaction-based assays in 685 participants including
459 IBD patients and 226 healthy volunteers. Study results revealed 434/459 (94.55%) IBD patients and 213/226 (94.25%) healthy subjects to be homozygous for the wild-type allele (TPMT*1/*1).
TPMT*1/*2 and TPMT *1/*3C genotypes were found in 4/459 (0.87%) and 7/459 (1.53%) IBD patients, respectively; in healthy volunteers they were not found. TPMT*1/*3A genotype was found in 14/459 (3.05%) IBD patients and 13/226 (5.75%) healthy subjects. Variant genotypes were statistically significantly more common in Crohn’s disease subgroup than in ulcerative colitis subgroup. The prevalence of variant genotypes was 23/338 (6.80%) in Crohn’s disease subgroup as compared with 2/121 (1.65%) in ulcerative colitis subgroup (χ2=4.59; p=0.032). In conclusion, the most frequently occurring nonfunctional TPMT allele in Croatian population is TPMT*3A. The overall frequency of mutant alleles in our population is statistically nonsignificantly lower when compared with other populations of Caucasian origin. The Crohn’s disease group had more mutant alleles than the ulcerative colitis group.
Keywords
Crohn’s disease – genetics; Colitis, ulcerative – genetics; Thiopurine-S-methyltransferase deficiency; Polymorphism, genetic
Hrčak ID:
161268
URI
Publication date:
1.3.2016.
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