Liu Qing-Xia, Chen Han-Chun, Liu Xin-Fa, Cao Yan-Fei, Zhang Ji, Liu Jia
Molecular Biology Research Center, Xiangya School of Medicine, Central South University, Changsha 410078, China.
Zhonghua Liu Xing Bing Xue Za Zhi. 2005 Dec;26(12):975-9.
Based on the distribution of genetic polymorphisms regarding phase I metabolic enzyme cytochrome P450 1A1 (CYP1A1) and phase II metabolic enzymes glutathione S-transferase GSTM1 and GSTT1 genotypes in acute leukemia patients and health controls among general population of Hunan in China, this study was to explore the relationship between these gene polymorphisms and the susceptibility to acute leukemia.
Using case-control methodology, we studied 204 healthy controls and 232 patients with acute leukemia, of which 112 patients were suffering acute lymphoblastic leukemia (ALL) and 120 with acute non-lymphoblastic leukemia (ANLL). The frequencies of the genotypes were detected by PCR and PCR-RFLP techniques.
The variation frequencies of CYP1A1 gene (Msp I polymorphisms, site 3801T-C variation) in ALL and ANLL groups were 74.1% and 70.8% respectively which were higher than 63.3% appeared in the healthy controls. However, the differences between patients (ALL or ANLL) and healthy controls were not statistically significant (P > 0.05 for both). The null genotype of GSTM1 (GSTM1 -/-) in ALL group was 60.7%, which was not significantly different from the controls (55.4%). However, GSTM1 -/- genotype in ANLL group was 68.3%, significantly different from the controls (P < 0.05). The null genotypes among GSTT1 (GSTT1 -/-) in ALL, ANLL and control group were 50.9%, 55.0% and 49.0% but their differences were not statistically significant (P > 0.05). The incidences of GSTM1 -/- and GSTT1 -/- combined genotype in ALL, ANLL and control group were 33.0%, 40.0% and 27.5%, of which the difference between ANLL group and control group was statistically significant (P < 0.05) and CYP1A1 gene heterozygous mutation type or homozygous mutation type combined with GSTM1 -/- and GSTT1 -/- increased the risk of ANLL (OR value 1.890, 95% CI: 1.084-3.295).
These results indicated that both the variation of CYP1A1 gene or GSTT1 -/- genotype alone might not be associated with the susceptibility of acute leukemia while GSTM1 -/- genotype alone or combined with GSTT1 -/- or the 3801 T-C variation of CYP1A1 gene were correlated with ANLL. These findings suggest that GSTM1 - / - genotype alone or in combination with other defective genotypes might serve as risk factors to the etiology of ANLL.
基于中国湖南普通人群中急性白血病患者和健康对照者中参与Ⅰ相代谢的细胞色素P450 1A1（CYP1A1）及参与Ⅱ相代谢的谷胱甘肽S-转移酶GSTM1和GSTT1基因多态性的分布情况，本研究旨在探讨这些基因多态性与急性白血病易感性之间的关系。
采用病例对照研究方法，我们研究了204名健康对照者和232例急性白血病患者，其中112例为急性淋巴细胞白血病（ALL）患者，120例为急性非淋巴细胞白血病（ANLL）患者。通过聚合酶链反应（PCR）和聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术检测基因型频率。
ALL组和ANLL组中CYP1A1基因（MspⅠ多态性，3801位点T-C变异）的变异频率分别为74.1%和70.8%，高于健康对照者中的63.3%。然而，患者（ALL或ANLL）与健康对照者之间的差异无统计学意义（两者P均>0.05）。ALL组中GSTM1的无效基因型（GSTM1 -/-）为60.7%，与对照组（55.4%）无显著差异。然而，ANLL组中GSTM1 -/-基因型为68.3%，与对照组有显著差异（P<0.05）。ALL组、ANLL组和对照组中GSTT1的无效基因型（GSTT1 -/-）分别为50.9%、55.0%和49.0%，但差异无统计学意义（P>0.05）。ALL组、ANLL组和对照组中GSTM1 -/-与GSTT1 -/-联合基因型的发生率分别为33.0%、40.0%和27.5%，其中ANLL组与对照组之间的差异有统计学意义（P<0.05），CYP1A1基因杂合突变型或纯合突变型与GSTM1 -/-和GSTT1 -/-联合增加了ANLL的发病风险（比值比1.890，95%可信区间：1.084-3.295）。
这些结果表明，单独的CYP1A1基因变异或GSTT1 -/-基因型可能与急性白血病易感性无关，而单独的GSTM1 -/-基因型或与GSTT1 -/-联合或CYP1A1基因的3801 T-C变异与ANLL相关。这些发现提示，单独的GSTM1 - / -基因型或与其他缺陷基因型联合可能是ANLL病因学的危险因素。
