CAJ | 학술논문

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。
목적：연구곡광감태전이매P1（glutathione S-transferase pi，GSTP1）기인다태성여인동급성림파세포백혈병（acute lymphoblastic leukemia，ALL）사용대제량갑안접령（high-dose methotrexate，HD-MTX）화료후불량반응적관계。방법：응용소식PCR（Nest PCR）、변성제도응효전영（denaturing gel gradient electrophoresis，DGGE）화DNA직접측서기술검측51례인동ALL GSTP1기인형화등위기인분포빈솔，안미국국립암증연구소적상규독성판정표준（NCICTCAE）대HD-MTX불량반응진행통계분석。결과：사사출3개GSTP1 SNPs위점즉rs1695（A313G）、rs1138272（G439T）화rs4891（T555C）。rs1695/rs4891다태성위점포괄32례（62.7%）야생형、16례（31.4%）잡합형화3례（5.9%）순합형，rs1138272다태성위점부포괄1례（2.0%）잡합형화1례（2.0%）순합형。3개SNPs위점등위기인빈솔분별위21.6%、2.9%화21.6%。GSTP1 rs1695/rs4891다태성위점중AG+GG/TC+CC기인형여외주혈혈홍단백감소유관（OR=0.25，95%CI=0.06～1.00，P=0.049），GSTP1 rs1695/rs4891다태성위점중AG+GG/TC+CC기인형여고위조환인위장독성발생유관（OR=0.125，95%CI=0.02～0.78，P=0.026）。결론：GSTP1 rs1695/rs4891다태성여ALL인동HD-MTX화료후외주혈혈홍단백강저이급중고위조ALL인동발생위장독성유관。
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.