title: Prevalence of mutations in thiopurine S-methyltransferase gene among Slovak IBD patients.
abstract: BACKGROUND
  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 hematopoetic 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 the particular inflammatory bowel disease (IBD) population.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  TPMT genetic polymorphisms (TPMT*2, TPMT*3A, TPMT*3B, TPMT*3C) were amplified using PCR and consequently genotyped on genetic analyzer. The allele frequencies of particular allelic variants were calculated and compared with other Caucasian populations reported so far.
  
  
  RESULTS
  Three hundred and thirty IBD patients were included; 196/132/2 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, only one patient was homozygous for TPMT*3A allele (0.3 %). The most prevalent mutant allele was TPMT*3A (3.2 %). The distribution of the most common allelic variants of TPMT gene among Slovak IBD patients were in accordance with previously reported prevalence in Caucasian populations.
  
  
  CONCLUSIONS
  This study shows the prevalence of TPMT genetic polymorphisms in the Slovak IBD patient`s population. As in other Caucasian populations, the most common mutant allelic variant is TPMT*3A, and the prevalence of homozygosity is relatively low (Tab. 3, Ref. 16).
authors.affiliation: Department of Gastroenterology, University Hospital, Bratislava, Slovakia.
authors.forename: B
authors.initials: B
authors.lastname: Desatova
authors.forename: T
authors.initials: T
authors.lastname: Hlavaty
authors.forename: D
authors.initials: D
authors.lastname: Balakova
authors.forename: I
authors.initials: I
authors.lastname: Pav
authors.forename: P
authors.initials: P
authors.lastname: Celec
authors.forename: M
authors.initials: M
authors.lastname: Gregus
authors.forename: M
authors.initials: M
authors.lastname: Zakuciova
authors.forename: M
authors.initials: M
authors.lastname: Hlista
authors.forename: M
authors.initials: M
authors.lastname: Horakova
authors.forename: L
authors.initials: L
authors.lastname: Kadasi
authors.forename: M
authors.initials: M
authors.lastname: Huorka
authors.forename: M
authors.initials: M
authors.lastname: Batovsky
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005828:Genetics, Population; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D055815:Young Adult
chemical_list: D008780:Methyltransferases; C022745:thiopurine methyltransferase