title: TPMT genetic variations in populations of the Russian Federation.
abstract: BACKGROUND
  Polymorphisms that reduce the activity of thiopurine S-methyltransferase (TPMT) cause adverse reactions to conventional doses of thiopurines, routinely used for antileukemic and immunosuppressive treatment. There are more than 20 variant alleles of TPMT that cause decreased enzymatic activity. We studied the most common variant alleles of TPMT and their frequency distribution in a large cohort of multiracial residents in the Russian Federation and compared their frequencies in children with and without malignancy to determine whether TPMT gene abnormality is associated with hematologic malignancy.
  
  
  METHODS
  The TPMT biochip was used to detect 6 TPMT single nucleotide polymorphisms (SNPs) corresponding to 7 TPMT-deficiency alleles (TPMT*2, TPMT*3A, TPMT*3B, TPMT*3C, TPMT*3D, TPMT*7, and TPMT*8). We analyzed allele frequencies in the whole cohort, the childhood cancer group, and the non-cancer group. We also characterized disease features and outcome according to the presence of TPMT SNPs in children with acute lymphoblastic leukemia (ALL).
  
  
  RESULTS
  Fifty-five (5.5%) study participants overall had heterozygous TPMT genotypes (1 variant and 1 wild-type allele): TPMT*1/*3A (n = 45; 4.5%), TPMT*1/*3C (n = 8; 0.8%), and TPMT*1/*2 (n = 2; 0.2%). TPMT SNPs were more frequent in children with hematologic malignancy than in other participants (7.5% vs. 4.0%, P = 0.02). We found no significant association between TPMT SNPs and ALL treatment outcome (median follow-up, 31.3 months).
  
  
  CONCLUSIONS
  TPMT*3A is the most prevalent variant allele in the Russian Federation. The estimated frequency of variant alleles in the study cohort (5.5%) was similar to that observed in the White populations in the U.S. and Eastern Europe.
authors.affiliation: Federal Research Center for Pediatric Hematology, Oncology, and Immunology, Moscow, Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Samochatova
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Chupova
authors.forename: Anastassia
authors.initials: A
authors.lastname: Rudneva
authors.forename: Olga
authors.initials: O
authors.lastname: Makarova
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Nasedkina
authors.forename: Olga E
authors.initials: OE
authors.lastname: Fedorova
authors.forename: Andrei S
authors.initials: AS
authors.lastname: Glotov
authors.forename: Zh
authors.initials: Zh
authors.lastname: Kozhekbaeva
authors.forename: Olga A
authors.initials: OA
authors.lastname: Maiorova
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Roumyantsev
authors.forename: Eugene Y
authors.initials: EY
authors.lastname: Krynetski
authors.forename: Natalia F
authors.initials: NF
authors.lastname: Krynetskaia
authors.forename: William E
authors.initials: WE
authors.lastname: Evans
authors.forename: Raul C
authors.initials: RC
authors.lastname: Ribeiro
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D019337:Hematologic Neoplasms / Q000235:genetics; D006801:Humans; D008297:Male; D008780:Methyltransferases / Q000172:deficiency / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D044469:Racial Groups / Q000235:genetics; D012426:Russia / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D008780:Methyltransferases; C022745:thiopurine methyltransferase