基于内镜检查人群的谷胱甘肽S-转移酶表型与基因变异及果蔬摄入量的关系

Glutathione S-transferase phenotypes in relation to genetic variation and fruit and vegetable consumption in an endoscopy-based population.

作者信息

Tijhuis Mariken J, Visker Marleen H P W, Aarts Jac M M J G, Peters Wilbert H M, Roelofs Hennie M J, den Camp Liesbeth Op, Rietjens Ivonne M C M, Boerboom Anne-Marie J F, Nagengast Fokko M, Kok Frans J, Kampman Ellen

机构信息

Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.

出版信息

Carcinogenesis. 2007 Apr;28(4):848-57. doi: 10.1093/carcin/bgl204. Epub 2006 Oct 27.

Abstract

High glutathione S-transferase (GST) activity may contribute to colorectal cancer prevention. Functional polymorphisms are known in the GSTM1, GSTT1, GSTA1 and GSTP1 genes. The influence of these GST polymorphisms and recent fruit and vegetable consumption on GST levels and activity has not been investigated simultaneously in a human population. Also, it is not clear if blood GST activity reflects rectal GST activity. Therefore, we determined GST polymorphisms in 94 patients scheduled for sigmoidoscopy. Rectal GST isoenzyme levels (GSTM1, GSTM2, GSTT1, GSTA and GSTP1) were measured by quantitative western blotting, and rectal and white blood cell total GST activities were measured spectrophotometrically using 1-chloro-2,4-dinitrobenzene (CDNB) as a substrate. Vegetable and fruit consumption was assessed by dietary record. As expected, the GSTM1 and GSTT1 deletion polymorphisms, and the GSTA1 g.-69C-->T polymorphism significantly affected the respective isoenzyme levels. Also, rectal GST isoenzyme levels differed between those with and without recent consumption of Alliaceae, Cucurbitaceae, Apiaceae and citrus fruit. Rectal GST activity, however, was not clearly influenced by fruit and vegetable consumption. It was most significantly determined by the GSTP1 c.313A-->G polymorphism; compared with the 313AA genotypes, the 313AG and 313GG genotypes showed 36 and 67 nmol/min/mg protein (P < 0.001) lower GST activity, respectively. The correlation between rectal and white blood cell GST activities was low (r = 0.40, P < 0.001), and the relevance of the various genetic and dietary factors appeared to differ between the two tissues. In conclusion, this study indicates that the GST enzyme system is influenced by both GST polymorphisms and consumption of fruits and vegetables. The latter appeared more important for individual rectal GST isoenzyme levels than for total GST activity, which could affect detoxification of isoenzyme-specific substrates. The study results do no support the use of white blood cell GST activity as a surrogate measure for rectal GST activity.

摘要

高谷胱甘肽S-转移酶(GST)活性可能有助于预防结直肠癌。已知GSTM1、GSTT1、GSTA1和GSTP1基因存在功能多态性。尚未在人群中同时研究这些GST多态性以及近期水果和蔬菜摄入量对GST水平和活性的影响。此外,血液GST活性是否反映直肠GST活性尚不清楚。因此,我们对94例计划进行乙状结肠镜检查的患者进行了GST多态性测定。通过定量蛋白质印迹法测量直肠GST同工酶水平(GSTM1、GSTM2、GSTT1、GSTA和GSTP1),并使用1-氯-2,4-二硝基苯(CDNB)作为底物通过分光光度法测量直肠和白细胞的总GST活性。通过饮食记录评估蔬菜和水果摄入量。正如预期的那样,GSTM1和GSTT1缺失多态性以及GSTA1基因g.-69C→T多态性显著影响各自的同工酶水平。此外,近期食用葱属、葫芦科、伞形科和柑橘类水果的人群与未食用者之间的直肠GST同工酶水平存在差异。然而,直肠GST活性并未明显受到水果和蔬菜摄入量的影响。它最主要由GSTP1基因c.313A→G多态性决定;与313AA基因型相比,313AG和313GG基因型的GST活性分别低36和67 nmol/分钟/毫克蛋白(P<0.001)。直肠和白细胞GST活性之间的相关性较低(r = 0.40,P<0.001),并且各种遗传和饮食因素在两种组织中的相关性似乎有所不同。总之,本研究表明GST酶系统受GST多态性和水果及蔬菜摄入量的影响。后者对个体直肠GST同工酶水平似乎比对总GST活性更重要,这可能会影响同工酶特异性底物的解毒作用。研究结果不支持将白细胞GST活性用作直肠GST活性的替代指标。

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