Human glutathione S-transferase P1 polymorphisms:: relationship to lung tissue enzyme activity and population frequency distribution
Human glutathione S-transferase P1 polymorphisms:: relationship to lung tissue enzyme activity and population frequency distribution
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DOI：
10.1093/carcin/19.2.275
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发表时间：
1998-02-01
期刊：
影响因子：
4.7
通讯作者：
Bell, DA
中科院分区：
文献类型：
--
作者：
Watson, MA;Stewart, RK;Bell, DA
用1-氯-2，4-二硝基苯（CDNB）标记法检测34例手术患者正常肺组织中谷胱甘肽S-转移酶（GST）活性，并对GST 1基因第5、6外显子的基因型进行分析。采用PCR-RFLP和直接测序法对这些样本进行基因分型，以检测第5外显子（Ile 105 Val）和第6外显子（Ala 114 Val）的多态性。GST酶活性显着较低的个人与105瓦尔等位基因。纯合的Ile/Ile样品（n = 18）具有74.9 +/-3.8mnol/mg/min的平均胞质CDNB缀合活性;杂合子（n = 13）的平均比活性为62.1 +/-4.2 nmol/mg/min，纯合子瓦尔/瓦尔（n = 3）的平均比活性为52.5 +/-4.5 nmol/mg/min。对于Ile/Ile基因型组测量的CDNB缀合活性与在Ile/瓦尔组中观察到的CDNB缀合活性显著不同（P = 0.03），并且与Ile/瓦尔和瓦尔/瓦尔基因型组合的CDNB缀合活性显著不同（P = 0.009）。平均GST活性值只是一贯较低的基因型含有105缬氨酸等位基因的个人，无论吸烟暴露。在密码子114的基因型也进行了评估，但平均GST活性与114缬氨酸等位基因的个人没有显着降低。在两个105 Ile和114 Val纯合的样本中发现了一个新的单倍型，并被确定为GST P1 *D。外显子5和外显子6多态性的频率在从欧洲裔美国人，非洲裔美国人和台湾人获得的样本中进行了测定。观察到的差异是非常显着的，这表明GST 1基因型相关的可能性，在癌症易感性和化疗反应的种族差异。
The association between glutathione S-transferase (GST) activity as measured by 1-chloro-2,4-dinitrobenzene (CDNB) conjugation and genotype at exon 5 and exon 6 of the human GSTP1 gene was investigated in normal lung tissue obtained from 34 surgical patients. These samples were genotyped for previously identified polymorphisms in exon 5 (Ile105Val) and exon 6 (Ala114Val) by PCR-RFLP and direct sequencing. GST enzyme activity was significantly lower among individuals with the 105 Val allele. Homozygous Ile/Ile samples (n = 18) had a mean cytosolic CDNB conjugating activity of 74.9 +/- 3.8 mnol/mg per min; heterozygotes (n = 13) had a mean specific activity of 62.1 +/- 4.2 nmol/mg per min and homozygous Val/Val (n = 3) had a mean specific activity of 52.5 +/- 4.5 nmol/mg mg per min. The CDNB conjugating activity measured for the Ile/Ile genotype group was significantly different from that observed in the Ile/Val group (P = 0.03), and from Ile/Val and Val/Val genotypes combined (P = 0.009). Mean GST activity values mere consistently lower in individuals with genotypes containing the 105 valine allele, regardless of smoking exposure. Genotypes at codon 114 were also assessed but the mean GST activity was not significantly lower in individuals with the 114 valine allele. A new haplotype, present in two samples who were homozygous 105Ile and had a 114Val, was identified and proposed as GSTP1*D. Frequencies of the exon 5 and exon 6 polymorphisms were determined in samples obtained from European-Americans, African-Americans and Taiwanese. The differences observed were highly significant suggesting the possibility of GSTP1 genotype-associated, ethnic differences in cancer susceptibility and chemotherapeutic response.