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 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).
  
  
  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 with 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 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 TPMT*3A allele (0.3 %). The most prevalent mutant allele was that of TPMT*3A (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.
  
  
  CONCLUSIONS
  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).
authors.affiliation: Department of Internal Medicine V, Division of Gastroenterology and Hepatology, University Hospital Bratislava Ruzinov, Slovakia. barboradesat@yahoo.com
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; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D018154:Slovakia; D055815:Young Adult
chemical_list: D008780:Methyltransferases; C022745:thiopurine methyltransferase
keywords: thiopurine S-methyltransferase, thiopurines toxicity, genetic polymorphisms.