廖清船,李晓蕾,刘思婷,张永,李天媛,仇锦春.MTHFR基因多态性及单体型与大剂量甲氨蝶呤化疗毒性反应的相关性研究[J].中华流行病学杂志,2012,33(7):735-739 |
MTHFR基因多态性及单体型与大剂量甲氨蝶呤化疗毒性反应的相关性研究 |
Association between the methylenetetrahydrofolate reductase gene polymorphisms and haplotype with toxicity response of high dose methotrexate chemotherapy |
收稿日期:2012-02-10 出版日期:2014-09-09 |
DOI: |
中文关键词: 亚甲基四氢叶酸还原酶 甲氨蝶呤 急性淋巴细胞白血病 单体型 |
英文关键词: Methylenetetrahydrofolate reductase Methotrexate Acute lymphoblastic leukemia Haplotype |
基金项目:本研究得到南京市医学科技发展项目(YKK10052)及南京市2011年度科技发展计划(药学项目(2011YX016)的支持 |
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中文摘要: |
目的 探讨亚甲基四氢叶酸还原酶(MTHFR)基因多态性及其单体型与急性淋巴细胞白血病患儿大剂量甲氨蝶呤(HDMTX)化疗毒性反应的相关性.方法 采用聚合酶链反应-限制性片段长度多态性方法对HDMTX化疗后出现毒性反应(n=61)和无毒性反应的患儿(n=36)MTHFR基因677C>T、1298A>C单核苷酸多态性(SNP)进行基因分型和单体型分析,并应用病例对照分析方法进行相关性研究.结果 MTHFR 677C>T不同基因型在两组患儿中的分布频率差异无统计学意义(x2=4.609,P=0.100).1298A>C不同基因型在两组患儿中的分布频率差异有统计学意义(x2=10.192,P=0.006),1298C等位基因(AC+CC基因型)携带者出现毒性反应的风险降低(OR=0.245,95%CI:0.099~ 0.607,P=0.002).677C>T与1298A>C存在着强连锁不平衡(D'=0.895),CC单体型携带者出现毒性反应的风险降低(OR=0.338,95%CI:0.155~ 0.738,P=0.005),而TA单体型携带者出现毒性反应的风险增加(OR=1.907,95%CI:1.045~3.482,P=0.035).结论 MTHFR 1298C等位基因及CC单体型可能是HDMTX毒性反应的保护因素,TA单体型可能是危险因素. |
英文摘要: |
Objective To investigate the association between single nucleotide polymorphisms (SNP) and its haplotypes of methylenetetrahydrofolate reductase (MTHFR) gene with high dose methotrexate (HDMTX)-induced toxicity in children with acute lymphoblastie leukemia (ALL).Methods HDMTX-treated children with ALL (1.2 to 14-years old) were selected from inpatient and followed for a retrospective study.The toxicity response of HDMTX chemotherapy was evaluated using WHO common toxicity criteria.Sixty-one patients with therapy-related toxicity and 36 patients without therapy-related toxicity were genotyped for 2 ShP (677C>T and 1298A>C) of the MTHFR gene by polymerase chain reaction-restriction fragment length polymorphism.Frequency of haplotypes and linkage disequilibrium of MTHFR gene were analyzed by SHEsis program.Results The distribution of MTHFR gene 677C>T polymorphism did not appeare different between groups with or without toxicity response (x2=4.609,P=0.100),but the 1298A>C polymorphism was significantly different (x2=10.192,P=0.006).Individuals who carried C allele (AC +CC genotype) had a decreased risk of toxicity response compared to AA genotype ( OR=0.245,95%CI:0.099-0.607,P=0.002).677C>T and 1298A>C polymorphisms showed strong linkage disequilibrium (D'=0.895 ).The CC haplotype was significantly associated with decreased risk of toxicity response (OR=0.338,95%CI:0.155-0.738,P=0.005),while the TA haplotype was significantly associated with the increased risk of toxicity response (OR=1.907,95% CI:1.045-3.482,P=0.035).Conclusion MTHFR gene 1298C allele and CC haplotype might serve as protective factors while TA haplotype as a risk factor for the susceptibility to toxicity response of HDMTX chemotherapy in children with ALL. |
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