Marinho Cláudia, Alho Irina, Arduíno Daniela, Falcão Luiz Menezes, Brás-Nogueira José, Bicho Manuel
Genetics Laboratory, Centre of Metabolism and Endocrinology, Lisbon Medical School, University of Lisbon, Portugal.
Biochem Biophys Res Commun. 2007 Feb 9;353(2):344-50. doi: 10.1016/j.bbrc.2006.12.019. Epub 2006 Dec 11.
The aim of this study is to investigate GSTM1, GSTT1 and MTHFR genetic polymorphisms and its relation with total plasma glutathione (tGSH) levels in hypertension. Genotype distributions of GSTM1 and GSTT1 deletion polymorphisms and C677T variant of MTHFR were examined in a sample of 94 hypertensive patients with congestive heart failure and 207 healthy unrelated Portuguese individuals using PCR techniques. Plasma GST activity was determined spectrophotometrically. The antioxidant status was evaluated by fluorometric assays of tGSH. Genotype distributions of GSTT1 (chi2 test; p < 0.01) and MTHFR (chi2 test; p < 0.01) differ significantly between control and hypertensive patients with a greater prevalence of "non-null GSTT1/M1" and CT (heterozygous) genotypes. Moreover, GST activity and tGSH were markedly decreased in hypertension but there is no correlation with the studied polymorphisms. GSH depletion confirmed the possible involvement of oxidative stress in this pathology. Deletion of GSTT1 gene might be considered as protective factor for hypertension.
本研究旨在调查高血压患者中谷胱甘肽S-转移酶M1(GSTM1)、谷胱甘肽S-转移酶T1(GSTT1)和亚甲基四氢叶酸还原酶(MTHFR)基因多态性及其与血浆总谷胱甘肽(tGSH)水平的关系。采用聚合酶链反应(PCR)技术,对94例伴有充血性心力衰竭的高血压患者和207名无亲缘关系的健康葡萄牙个体样本进行GSTM1和GSTT1缺失多态性以及MTHFR基因C677T变异的基因型分布检测。用分光光度法测定血浆谷胱甘肽S-转移酶(GST)活性。通过tGSH荧光测定法评估抗氧化状态。在对照组和高血压患者之间,GSTT1(卡方检验;p<0.01)和MTHFR(卡方检验;p<0.01)的基因型分布存在显著差异,“非无效GSTT1/M1”和CT(杂合子)基因型的患病率更高。此外,高血压患者的GST活性和tGSH显著降低,但与所研究的多态性无相关性。谷胱甘肽(GSH)耗竭证实氧化应激可能参与了这一病理过程。GSTT1基因缺失可能被视为高血压的保护因素。