IR@PKUHSC  > 北京大学基础医学院  > 药理学系
学科主题基础医学
Influence of genetic polymorphisms of FPGS, GGH, and MTHFR on serum methotrexate levels in Chinese children with acute lymphoblastic leukemia
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
2014-08-01
DOI10.1007/s00280-014-2507-8
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
资助者Beijing Shijitan Hospital, Capital Medical University ; Beijing Shijitan Hospital, Capital Medical University
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
资助者Beijing Shijitan Hospital, Capital Medical University ; Beijing Shijitan Hospital, Capital Medical University
WOS记录号WOS:000339825000008
引用统计
被引频次:5[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/66086
专题北京大学基础医学院_药理学系
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
推荐引用方式
GB/T 7714
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.
APA Wang, Shu-mei,Sun, Lu-lu,Zeng, Wei-xin,Wu, Wan-shui,&Zhang, Guo-liang.(2014).Influence of genetic polymorphisms of FPGS, GGH, and MTHFR on serum methotrexate levels in Chinese children with acute lymphoblastic leukemia.CANCER CHEMOTHERAPY AND PHARMACOLOGY,74(2),283-289.
MLA Wang, Shu-mei,et al."Influence of genetic polymorphisms of FPGS, GGH, and MTHFR on serum methotrexate levels in Chinese children with acute lymphoblastic leukemia".CANCER CHEMOTHERAPY AND PHARMACOLOGY 74.2(2014):283-289.
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