Genetic variations and haplotype structures of the glutathione S-transferase genes, GSTT1 and GSTM1, in a Japanese patient population.
Genetic variations and haplotype structures of the glutathione S-transferase genes, GSTT1 and GSTM1, in a Japanese patient population.
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日本患者群体中谷胱甘肽 S-转移酶基因 GSTT1 和 GSTM1 的遗传变异和单倍型结构。
DOI：
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发表时间：
2009
影响因子：
2.1
通讯作者：
J. Sawada
中科院分区：
文献类型：
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作者：
Naoko Tatewaki;K. Maekawa;N. Katori;K. Kurose;N. Kaniwa;N. Yamamoto;H. Kunitoh;Y. Ohe;H. Nokihara;I. Sekine;T. Tamura;Teruhiko Yoshida;N. Saijo;Yoshiro Saito;J. Sawada
谷胱甘肽S-转移酶（GST）在许多合成化学品（包括抗癌药物）的II相生物转化中起着至关重要的作用。据报道，GSTT 1和GSTM 1的缺失多态性与癌症风险增加以及对化疗药物的反应改变有关，尽管存在争议。在这项研究中，为了阐明GSTT 1和GSTM 1的单倍型结构，在194名接受铂类化疗的日本癌症患者中鉴定了遗传变异。GSTT 1（*）0/（*）0或null）和GSTM 1（*）0/（*）0或null）缺失的纯合子分别占47.4%和47.9%，GSTT 1和GSTM 1基因型同时缺失的占23.2%。从携带GSTT 1和GSTM 1基因的纯合子（+/+）和杂合子（（*）0/+）患者中鉴定出GSTT 1的6个单核苷酸多态性（SNP）和GSTM 1的23个SNP。在GSTT 1，226 C>A（Arg 76 Ser）和GSTM 1，519 C>G（Asn 173 Lys，（*）B）中发现了一个新的SNP，其频率分别为0.003和0.077。使用检测到的变异，GSTT 1和GSTM 1单倍型进行鉴定/推断。GSTT 1和GSTM 1分别有3种和6种常见单倍型（N ≥ 10），占推测单倍型的95%以上。这一信息将是有用的外源性药物，包括抗癌药物的药物基因组学研究。
Glutathione S-transferases (GSTs) play a vital role in phase II biotransformation of many synthetic chemicals including anticancer drugs. Deletion polymorphisms in GSTT1 and GSTM1 are reportedly associated, albeit controversial, with an increased risk in cancer as well as with altered responses to chemotherapeutic drugs. In this study, to elucidate the haplotype structures of GSTT1 and GSTM1, genetic variations were identified in 194 Japanese cancer patients who received platinum-based chemotherapy. Homozygotes for deletion of GSTT1 (GSTT1(*)0/(*)0 or null) and GSTM1 (GSTM1(*)0/(*)0 or null) were found in 47.4% and 47.9% of the patients, respectively, while 23.2% of the patients had both GSTT1 null and GSTM1 null genotypes. From homozygous (+/+) and heterozygous ((*)0/+) patients bearing GSTT1 and GSTM1 genes, six single nucleotide polymorphisms (SNPs) for GSTT1 and 23 SNPs for GSTM1 were identified. A novel SNP in GSTT1, 226C>A (Arg76Ser), and the known SNP in GSTM1, 519C>G (Asn173Lys, (*)B), were found at frequencies of 0.003 and 0.077, respectively. Using the detected variations, GSTT1 and GSTM1 haplotypes were identified/inferred. Three and six common haplotypes (N> or =10) in GSTT1 and GSTM1, respectively, accounted for most (>95%) inferred haplotypes. This information would be useful in pharmacogenomic studies of xenobiotics including anticancer drugs.
影响因子：
5.9
作者：
LISTOWSKY, I;ABRAMOVITZ, M;NIITSU, Y
通讯作者：
NIITSU, Y