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学科主题: 基础医学
题名:
Influence of genetic polymorphisms of FPGS, GGH, and MTHFR on serum methotrexate levels in Chinese children with acute lymphoblastic leukemia
作者: Wang, Shu-mei1; Sun, Lu-lu1; Zeng, Wei-xin1; Wu, Wan-shui2; Zhang, Guo-liang3
关键词: Acute lymphoblastic leukemia ; Methotrexate ; Folylpolyglutamate synthase ; Gamma-glutamyl hydrolase ; Methylenetetrahydrofolate reductase ; Single-nucleotide polymorphisms
刊名: CANCER CHEMOTHERAPY AND PHARMACOLOGY
发表日期: 2014-08-01
DOI: 10.1007/s00280-014-2507-8
卷: 74, 期:2, 页:283-289
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology ; Pharmacology & Pharmacy
研究领域[WOS]: Oncology ; Pharmacology & Pharmacy
关键词[WOS]: HIGH-DOSE METHOTREXATE ; METHYLENETETRAHYDROFOLATE REDUCTASE GENE ; RHEUMATOID-ARTHRITIS PATIENTS ; TOXICITY ; EFFICACY ; POLYGLUTAMATES ; RESISTANCE ; PATHWAY
英文摘要:

To investigate the correlation between common genetic polymorphisms of folylpolyglutamate synthase (FPGS), gamma-glutamyl hydrolase (GGH), and methylenetetrahydrofolate reductase (MTHFR) and serum levels of methotrexate (MTX) in Chinese children with acute lymphoblastic leukemia (ALL).

Ninety-one children with ALL who received high-dose MTX were recruited. The polymorphisms FPGS (rs1544105 G > A), GGH (rs3758149 C > T), and MTHFR (rs1801133 C > T) were genotyped through polymerase chain reaction-restriction fragment length polymorphism analysis. Serum MTX was measured by fluorescence polarization immunoassay. The association between targeted polymorphisms and MTX concentration-to-dose (C/D) ratios was assessed, and between targeted polymorphisms and the percent of MTX above the therapeutic threshold (40 A mu mol/L).

The minor allele frequencies of rs1544105 G (34.1 %), rs3758149 T (19.2 %), and rs1801133 C (48.4 %) observed in our population were significantly lower than those reported for European populations (64.2, 30.8, and 69.0 %, respectively). The association between the GGH rs3758149 polymorphism and MTX C/D was gender-specific; in girls, the MTX C/D at 24 h of GGH rs3758149 CC carriers (12.09 mu mol/L per g/m(2)) was significantly lower than that of CT or TT carriers (16.80 mu mol/L per g/m(2)). The percent of serum MTX above the therapeutic threshold in GGH rs3758149 CC carriers (18.3 %) was significantly lower than that of CT and TT carriers (38.7 %). The MTX C/D ratios at 24 h and the percent of MTX > 40 A mu mol/L for the A-T-T (three variant alleles) haplotype were significantly higher than those for other haplotypes combined (P < 0.05).

These data indicate that FPGS rs1544105, GGH rs3758149, and MTHFR rs1801133 polymorphisms contribute to the variability of MTX pharmacokinetics, and their genotyping may be useful to reduce toxicities associated with MTX therapy.

语种: 英语
所属项目编号: 2012-C03
项目资助者: Beijing Shijitan Hospital, Capital Medical University
WOS记录号: WOS:000339825000008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66086
Appears in Collections:基础医学院_药理学系_期刊论文

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作者单位: 1.Capital Med Univ, Dept Pharm, Beijing Shijitan Hosp, Beijing, Peoples R China
2.Capital Med Univ, Beijing Shijitan Hosp, Dept Pediat, Beijing, Peoples R China
3.Beijing Univ, Dept Pharmacol, Basic Med Sch, Beijing 100871, Peoples R China

Recommended Citation:
Wang, Shu-mei,Sun, Lu-lu,Zeng, Wei-xin,et al. Influence of genetic polymorphisms of FPGS, GGH, and MTHFR on serum methotrexate levels in Chinese children with acute lymphoblastic leukemia[J]. CANCER CHEMOTHERAPY AND PHARMACOLOGY,2014,74(2):283-289.
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