title: Distribution of TPMT risk alleles for thiopurine [correction of thioupurine] toxicity in the Israeli population.
abstract: OBJECTIVE
  Individuals with intermediate or no thiopurine S-methyltransferase (TPMT) activity are at risk of hematotoxicity when treated with standard doses of thiopurines, thus, pretreatment identification of these individuals is of major importance. The purpose of this study was to determine the frequency and distribution of TPMT polymorphic variants, known to functionally impair TPMT activity, in the highly heterogeneous Israeli population.
  
  
  METHODS
  TPMT genotyping of individuals representing three major demographic groups in Israel was carried out by PCR restriction fragment length polymorphism and high-resolution melting.
  
  
  RESULTS
  Frequencies of TPMT risk alleles differed significantly among the screened Israeli subpopulations: Druze showed fivefold and twofold higher frequencies than Jews and Moslems, respectively. Specifically, allelic frequencies of TPMT*3A were 0.73% (95% CI 0.34-1.45%), 0.79% (95% CI 0.16-2.39%), and 3.19% (95% CI 1.78-5.58%) in Jews, Moslems, and Druze, respectively. Although not found in Jews, TPMT*3C was found at an allelic frequency of 1.05% (95% CI 0.31-2.76%) and 0.75% (95% CI 0.02-2.84%) in Moslems and Druze. TPMT*2 and TPMT*3B were not detected in any of the Israeli subpopulations studied.
  
  
  CONCLUSIONS
  These data indicate that the Israeli population displays a distinct TPMT genetic variability that is comprised of a mix of three major genetically diverse subpopulations, each with its unique TPMT allelic frequency distribution pattern and likelihood of developing an adverse reaction to thiopurine drugs.
authors.affiliation: Center for Translational Genetics, B. Rappaport Institute for Research in the Medical Sciences, Faculty of Medicine, Technion - Israel Institute of Technology and Rambam Health Care Campus, Haifa, Israel. efrati@tx.technion.ac.il
authors.forename: Edna
authors.initials: E
authors.lastname: Efrati
authors.forename: Lior
authors.initials: L
authors.lastname: Adler
authors.forename: Norberto
authors.initials: N
authors.lastname: Krivoy
authors.forename: Eli
authors.initials: E
authors.lastname: Sprecher
mesh_terms: D000483:Alleles; D001379:Azathioprine / Q000633:toxicity; D005006:Ethnicity; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007557:Israel; D008297:Male; D015122:Mercaptopurine / Q000633:toxicity; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011687:Purines / Q000633:toxicity*; D013438:Sulfhydryl Compounds / Q000633:toxicity*; D013866:Thioguanine / Q000633:toxicity
chemical_list: D007166:Immunosuppressive Agents; D011687:Purines; D013438:Sulfhydryl Compounds; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D013866:Thioguanine; D001379:Azathioprine