谷胱甘肽转移酶P1基因多态性与儿童ALL HD-MTX不良反应的关系  

Association between glutathione S-transferase pi gene polymorphism and adverse reaction of high-dose methotrexate in children with acute lymphoblastic leukemia

作　　者：任艳飞[1] 袁秀丽[2] 岳丽杰[1] 邹泽巧 谢偲[1] 丁慧[1] 宋萍[3] 刘畅[1] 

机构地区：[1]遵义医学院附属深圳市儿童医院儿科研究所,广东省深圳市518026 [2]遵义医学院附属深圳市儿童医院血液科,广东省深圳市518026 [3]遵义医学院附属深圳市儿童医院急诊科,广东省深圳市518026

出　　处：《中国肿瘤临床》2014年第21期1358-1362,共5页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金项目(编号:30471830);深圳市科技计划项目(编号:201101011)资助~~

摘　　要：目的：研究谷胱甘肽转移酶P1（glutathione S-transferase pi，GSTP1）基因多态性与儿童急性淋巴细胞白血病（acute lymphoblastic leukemia，ALL）使用大剂量甲氨蝶呤（high-dose methotrexate，HD-MTX）化疗后不良反应的关系。方法：应用巢式PCR（Nest PCR）、变性梯度凝胶电泳（denaturing gel gradient electrophoresis，DGGE）和DNA直接测序技术检测51例儿童ALL GSTP1基因型和等位基因分布频率，按美国国立癌症研究所的常规毒性判定标准（NCICTCAE）对HD-MTX不良反应进行统计分析。结果：筛查出3个GSTP1 SNPs位点即rs1695（A313G）、rs1138272（G439T）和rs4891（T555C）。rs1695/rs4891多态性位点包括32例（62.7%）野生型、16例（31.4%）杂合型和3例（5.9%）纯合型，rs1138272多态性位点仅包括1例（2.0%）杂合型和1例（2.0%）纯合型。3个SNPs位点等位基因频率分别为21.6%、2.9%和21.6%。GSTP1 rs1695/rs4891多态性位点中AG＋GG/TC＋CC基因型与外周血血红蛋白减少有关（OR=0.25，95%CI=0.06～1.00，P=0.049），GSTP1 rs1695/rs4891多态性位点中AG＋GG/TC＋CC基因型与高危组患儿胃肠毒性发生有关（OR=0.125，95%CI=0.02～0.78，P=0.026）。结论：GSTP1 rs1695/rs4891多态性与ALL儿童HD-MTX化疗后外周血血红蛋白降低以及中高危组ALL儿童发生胃肠毒性有关。Objective：To investigate the association between glutathione S-transferase pi （GSTP1） gene polymorphism and toxici-ties related to high-dose methotrexate （HD-MTX） in children with acute lymphoblastic leukemia （ALL）. Methods：GSTP1 genotypes and allelic frequencies in 51 children with ALL were determined by Nest PCR, denaturing gel gradient electrophoresis （DGGE）, and DNA sequencing. HD-MTX adverse reactions were analyzed using the National Cancer Institute Common Toxicity Criteria （NCICTC）. Results：We identified three SNPs of GSTP1, including rs1695 （A313G）, rs1138272 （G439T）, and rs4891 （T555C）. The wild types, het-erozygous types, and homozygous types of GSTP1 rs1695/rs4891 polymorphisms were detected in 32 cases （62.7%）, 16 cases （31.4%）, and 3 cases （5.9%）, respectively. GSTP1 rs1695/rs4891 polymorphisms included only one heterozygous type and one homozygous type. The allele frequencies of the three SNPs were 21.6%, 2.9%, and 21.6%. The AG＋GG/TC＋CC genotype of GSTP1 rs1695/rs4891 was associated with decrease in the odds of peripheral hemoglobin （OR=0.25, 95%CI=0.06-1.00, P=0.049）. The AG＋GG/TC＋CC genotype of GSTP1 rs1695/rs4891 in standard and intermediate-risk ALL children was significantly correlated with higher odds of gastrointesti-nal toxicity （OR=0.125, 95%CI=0.02-0.78, P=0.026）. Conclusion：GSTP1 rs1695 （A313G）/rs4891 （T555C） gene polymorphism is as-sociated with the reduction of peripheral hemoglobin in ALL children and with the odds of gastrointestinal toxicity in standard and inter-mediate-risk ALL children who receive high-dose methotrexate.

关 键 词：谷胱甘肽转移酶 基因多态性 急性淋巴细胞白血病 甲氨蝶呤 不良反应 

分 类 号：R733.71[医药卫生—肿瘤]