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菲律宾急性淋巴细胞白血病儿童中GSTT1、GSTM1和NQO1(609C>T)的患病率。

Prevalence of GSTT1, GSTM1 and NQO1 (609C>T) in Filipino children with ALL (acute lymphoblastic leukaemia).

作者信息

Rimando Marilyn G, Chua Mary N, Yuson Ernesto d'J, de Castro-Bernas Gloria, Okamoto Takashi

机构信息

Department of Biological Sciences, College of Science, University of Santo Tomas, Manila, The Philippines.

出版信息

Biosci Rep. 2008 Jun;28(3):117-24. doi: 10.1042/BSR20070010.

Abstract

In the present paper, we examined the incidence of polymorphic genes involved with the detoxification of exogenous chemicals, including carcinogens, namely GSTT1 (glutathione transferase theta1), GSTM1 (glutathione transferase micro1) and NQO1 (NAD(P)H:quinone oxidoreductase 1) in 60 Filipino paediatric patients with ALL (acute lymphoblastic leukaemia). We found a significantly high incidence of the GSTM1 null genotype in ALL children (71.7%) compared with 51.7% in the control group of children (P<0.05). The GSTT1 null genotype was observed in 35.0% and 33.3% of the ALL cases and the control subjects respectively, with no significant difference. Screening for NQO1 (609C>T) mutant alleles showed a high incidence of the NQO1 C/C genotype (NQO1 homozygous wild-type allele genotype) in 60.0% of ALL cases and was significantly higher than in the control group (23.3%) (P<0.01). These GSTM1 null and NQO1 wild-type genotypes are independently associated with the risk of ALL in Filipino patients. When these two genotypes, GSTM1 null and NQO1 C/C, were combined, the hazard rate for childhood leukaemia was significantly increased (P<0.001). We also noticed that the incidences of GSTM1 null mutations and the NQO1 C/C genotype were significantly higher among Filipinos. These findings suggest a possible role of the GSTM1 null and NQO1 C/C genotypes in the susceptibility of paediatric ALL cases in the Philippines.

摘要

在本论文中,我们检测了60例菲律宾急性淋巴细胞白血病(ALL)儿科患者中涉及外源性化学物质(包括致癌物)解毒的多态性基因,即谷胱甘肽转移酶θ1(GSTT1)、谷胱甘肽转移酶μ1(GSTM1)和NAD(P)H:醌氧化还原酶1(NQO1)的发生率。我们发现,ALL儿童中GSTM1无效基因型的发生率显著较高(71.7%),而对照组儿童中的发生率为51.7%(P<0.05)。ALL病例和对照受试者中GSTT1无效基因型的发生率分别为35.0%和33.3%,无显著差异。对NQO1(609C>T)突变等位基因的筛查显示,60.0%的ALL病例中NQO1 C/C基因型(NQO1纯合野生型等位基因基因型)的发生率较高,且显著高于对照组(23.3%)(P<0.01)。这些GSTM1无效和NQO1野生型基因型与菲律宾患者患ALL的风险独立相关。当这两种基因型,即GSTM1无效和NQO1 C/C组合时,儿童白血病的危险率显著增加(P<0.001)。我们还注意到,菲律宾人中GSTM1无效突变和NQO1 C/C基因型的发生率显著更高。这些发现表明,GSTM1无效和NQO1 C/C基因型在菲律宾儿科ALL病例的易感性中可能起作用。

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