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TPMT genetic variations in populations of the Russian Federation
Author(s) -
Samochatova Elena V.,
Chupova Natalia V.,
Rudneva Anastassia,
Makarova Olga,
Nasedkina Tatyana V.,
Fedorova Olga E.,
Glotov Andrei S.,
Kozhekbaeva Zh.,
Maiorova Olga A.,
Roumyantsev Alexander G.,
Krynetski Eugene Y.,
Krynetskaia Natalia F.,
Evans William E.,
Ribeiro Raul C.
Publication year - 2009
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.21837
Subject(s) - thiopurine methyltransferase , medicine , pediatric cancer , single nucleotide polymorphism , allele , allele frequency , cohort , malignancy , genotype , cancer , genetics , oncology , disease , biology , azathioprine , gene
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. Procedure 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. Pediatr Blood Cancer 2009;52:203–208. © 2008 Wiley‐Liss, Inc.