Hattori Hiroyoshi, Suminoe Aiko, Wada Morimasa, Koga Yuhki, Kohno Kimitoshi, Okamura Jun, Hara Toshiro, Matsuzaki Akinobu
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
Leuk Res. 2007 Dec;31(12):1633-40. doi: 10.1016/j.leukres.2007.04.009. Epub 2007 Jun 12.
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.
本研究的目的是确定多药耐药基因1（MDR1）的多态性是否与儿童急性淋巴细胞白血病（ALL）的发生有关。对157例ALL患者和96例健康儿童检测了MDR1基因多态性，即-2352 G>A、-934A>G、-692T>C（5'调控区）和3435C>T（第26外显子）。使用正常外周血单个核细胞对54名健康个体的MDR1 mRNA量进行定量，以评估每种多态性对基因表达的影响。ALL患者中-2352 G>A的G/G基因型频率显著高于对照组（74/109对52/96，p=0.04）。3435C>T的T/T基因型频率在ALL中也显著更高（29/118对10/96，p=0.006）。在使用5'调控位点的单倍型分析中，某一单倍型的频率在ALL中高于对照组（59/90对42/88，p=0.048）。当在不同年龄组中检测-2352G>A时，发现6岁及以上患者的G/G基因型频率比对照组更高（42/51对52/96，p=0.0014），而在较年轻年龄组中未观察到差异。-2352 G>A的G/G或G/A基因型的MDR1 mRNA量显著高于A/A基因型（p=0.04）。本研究表明，MDR1的遗传背景可能与儿童ALL的发生有关，可能是由于基因多态性导致MDR1基因发生定量变化。
