Regulatory polymorphisms of multidrug resistance 1 (MDR1) gene are associated with the development of childhood acute lymphoblastic leukemia

Hiroyoshi Hattori, Aiko Suminoe, Morimasa Wada, Yuhki Koga, Kimitoshi Kohno, Jun Okamura, Toshiro Hara, Akinobu Matsuzaki

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Abstract

The aim of this study is to determine whether the polymorphisms of the MDR1 gene are associated with the development of childhood acute lymphoblastic leukemia (ALL). The MDR1 gene polymorphisms, -2352 G > A, -934A > G, -692T > C (5′ regulatory region) and 3435C > T (exon 26), were examined in 157 ALL patients and 96 healthy children. The amounts of MDR1 mRNA were quantified in 54 healthy individuals using normal peripheral blood mononuclear cells to evaluate the effect of each polymorphism on the gene expression. The frequency of the G/G genotype of the -2352 G > A was significantly higher in ALL than in controls (74/109 versus 52/96, p = 0.04). The frequency of the T/T genotype of the 3435C > T was also significantly higher in ALL (29/118 versus 10/96, p = 0.006). In a haplotype analysis using the 5′ regulatory sites, the frequency of a certain haplotype was higher in ALL than in controls (59/90 versus 42/88, p = 0.048). When the -2352G > A was examined in different age groups, patients aged six or older were found to have the G/G genotype more frequently than the controls (42/51 versus 52/96, p = 0.0014), while no difference was observed in the younger age group. The amounts of MDR1 mRNA were significantly higher in either G/G or G/A genotype of the -2352 G > A than in A/A genotype (p = 0.04). The present study suggests that the genetic background of MDR1 may be associated with the development of childhood ALL, possibly due to a quantitative change in the MDR1 gene resulting from genetic polymorphisms.

Original languageEnglish
Pages (from-to)1633-1640
Number of pages8
JournalLeukemia Research
Volume31
Issue number12
DOIs
Publication statusPublished - Dec 1 2007

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MDR Genes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Genotype
Multiple Drug Resistance
Haplotypes
Age Groups
Messenger RNA
Nucleic Acid Regulatory Sequences
Genetic Polymorphisms
Exons
Blood Cells
Gene Expression

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

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Regulatory polymorphisms of multidrug resistance 1 (MDR1) gene are associated with the development of childhood acute lymphoblastic leukemia. / Hattori, Hiroyoshi; Suminoe, Aiko; Wada, Morimasa; Koga, Yuhki; Kohno, Kimitoshi; Okamura, Jun; Hara, Toshiro; Matsuzaki, Akinobu.

In: Leukemia Research, Vol. 31, No. 12, 01.12.2007, p. 1633-1640.

Research output: Contribution to journalArticle

Hattori, Hiroyoshi ; Suminoe, Aiko ; Wada, Morimasa ; Koga, Yuhki ; Kohno, Kimitoshi ; Okamura, Jun ; Hara, Toshiro ; Matsuzaki, Akinobu. / Regulatory polymorphisms of multidrug resistance 1 (MDR1) gene are associated with the development of childhood acute lymphoblastic leukemia. In: Leukemia Research. 2007 ; Vol. 31, No. 12. pp. 1633-1640.
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abstract = "The aim of this study is to determine whether the polymorphisms of the MDR1 gene are associated with the development of childhood acute lymphoblastic leukemia (ALL). The MDR1 gene polymorphisms, -2352 G > A, -934A > G, -692T > C (5′ regulatory region) and 3435C > T (exon 26), were examined in 157 ALL patients and 96 healthy children. The amounts of MDR1 mRNA were quantified in 54 healthy individuals using normal peripheral blood mononuclear cells to evaluate the effect of each polymorphism on the gene expression. The frequency of the G/G genotype of the -2352 G > A was significantly higher in ALL than in controls (74/109 versus 52/96, p = 0.04). The frequency of the T/T genotype of the 3435C > T was also significantly higher in ALL (29/118 versus 10/96, p = 0.006). In a haplotype analysis using the 5′ regulatory sites, the frequency of a certain haplotype was higher in ALL than in controls (59/90 versus 42/88, p = 0.048). When the -2352G > A was examined in different age groups, patients aged six or older were found to have the G/G genotype more frequently than the controls (42/51 versus 52/96, p = 0.0014), while no difference was observed in the younger age group. The amounts of MDR1 mRNA were significantly higher in either G/G or G/A genotype of the -2352 G > A than in A/A genotype (p = 0.04). The present study suggests that the genetic background of MDR1 may be associated with the development of childhood ALL, possibly due to a quantitative change in the MDR1 gene resulting from genetic polymorphisms.",
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AU - Kohno, Kimitoshi

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AU - Hara, Toshiro

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