CAJ | 학술논문

目的：研究丝氨酸羟甲基转移酶1（serine hydroxymethyltransferase 1，SHMT1）基因多态性与急性淋巴细胞白血病（acute lymphocytic leukemia，ALL）儿童大剂量甲氨蝶呤（high-dose methotrexate，HD-MTX）不良反应的相关性。方法：本研究以51例接受HD-MTX化疗的ALL患儿为研究对象，统计分析其应用HD-MTX后产生的临床表现；提取mRNA后逆转录为cDNA，利用变性梯度凝胶电泳（denaturing gradient gel electrophoresis，DGGE）结合DNA测序检测SHMT1多态性（rs1979277、rs3783、rs1979276、rs12952556），并分析其与HD-MTX不良反应的关系。结果：接受HD-MTX化疗的ALL患儿产生的严重不良反应主要表现为中性粒细胞减少和肝功能损害。rs3783（C>G）、rs1979276（C>T）、rs12952556（A>G）及rs1979277（C>T）的基因型分布情况相同，rs1979277多态性与中性粒细胞减少的发生风险无关（P>0.05），但其CT及TT基因型可以降低肝功能损害的发生风险（CT：OR=0.129，95%CI：0.020～0.817，P=0.03；TT：OR=0.103，95%CI：0.017～0.620，P=0.013）。结论：rs1979277、rs3783、rs1979276及rs12952556的联合作用与中性粒细胞减少的发生无关，但它们之中一个或多个位点可能降低肝功能损害的发生。
목적：연구사안산간갑기전이매1（serine hydroxymethyltransferase 1，SHMT1）기인다태성여급성림파세포백혈병（acute lymphocytic leukemia，ALL）인동대제량갑안접령（high-dose methotrexate，HD-MTX）불량반응적상관성。방법：본연구이51례접수HD-MTX화료적ALL환인위연구대상，통계분석기응용HD-MTX후산생적림상표현；제취mRNA후역전록위cDNA，이용변성제도응효전영（denaturing gradient gel electrophoresis，DGGE）결합DNA측서검측SHMT1다태성（rs1979277、rs3783、rs1979276、rs12952556），병분석기여HD-MTX불량반응적관계。결과：접수HD-MTX화료적ALL환인산생적엄중불량반응주요표현위중성립세포감소화간공능손해。rs3783（C>G）、rs1979276（C>T）、rs12952556（A>G）급rs1979277（C>T）적기인형분포정황상동，rs1979277다태성여중성립세포감소적발생풍험무관（P>0.05），단기CT급TT기인형가이강저간공능손해적발생풍험（CT：OR=0.129，95%CI：0.020～0.817，P=0.03；TT：OR=0.103，95%CI：0.017～0.620，P=0.013）。결론：rs1979277、rs3783、rs1979276급rs12952556적연합작용여중성립세포감소적발생무관，단타문지중일개혹다개위점가능강저간공능손해적발생。
Objective:To investigate the correlation between polymorphisms of serine hydroxymethyltransferase1 gene and the adverse reactions of high-dose methotrexate (HD-MTX) in children with acute lymphoblastic leukemia (ALL). Methods:A total of 51 patients with ALL were treated with HD-MTX, and clinical manifestations after HD-MTX treatment were evaluated retrospectively. cD-NA was obtained from mRNA. The polymorphisms of SHMT1 gene containing rs1979277, rs3783, rs1979276, and rs12952556 sites were tested by denaturing gradient gel electrophoresis and direct sequencing. Effects of SHMT1 gene polymorphisms on HD-MTX ad-verse reactions were evaluated. Results:Severe adverse reactions in ALL patients treated with HD-MTX appeared to be mainly neutro-penia and hepatoadverse reactions. The frequency distributions of rs3783 (C>G), rs1979276 (C>T), rs12952556 (A>G), and rs1979277 (C>T) were the same. The polymorphisms of rs1979277 showed no correlation with neutropenia (P>0.05) but rs1979277 CT and TT genotypes were correlated with hepatoadverse reactions (CT: OR=0.129, 95% CI: 0.020 to 0.817, P=0.03; TT: OR=0.103, 95% CI:0.017 to 0.620, P=0.013). Conclusion: No correlation was found between the combination of rs1979277, rs3783, rs1979276, rs12952556, and neutropenia, but one or more of these loci may reduce the risk of hepatoadverse reactions.