Zivković Maja, Stanković Aleksandra, Djurić Tamara, Končar Igor, Kolaković Ana, Djurdjević Vladimir, Davidović Lazar, Alavantić Dragan
Institute of Nuclear Sciences "VINCA", Laboratory for Radiobiology and Molecular Genetics -080, University of Belgrade, P.O. Box 522, 11000, Belgrade, Serbia,
Mol Biol Rep. 2014 Feb;41(2):1157-64. doi: 10.1007/s11033-013-2962-z. Epub 2014 Jan 10.
Glutathione S-transferases (GSTs) carry out a wide range of functions in cells, such as detoxification of endogenous compounds, removal of reactive oxygen species, and even catalysis of reactions in metabolic pathways beyond detoxification. Based on previous research, GSTM1 and GSTT1 might modify the risk of atherosclerosis. The aim of our study was to analyze the possible association of GSTM1 and GSTT1 gene polymorphisms with the occurrence of carotid plaque (CP); and biochemical parameters of oxidative stress, lipid profile and inflammation, in 346 consecutive patients with advanced atherosclerosis that underwent endarterectomy. A multiplex polymerase chain reaction (PCR) method was used to detect the deletions in GSTM1 and GSTT1 genes in the genomic DNA in 346 patients and 330 controls. The adjusted OR for CP presence (adjusted for age, gender, smoking, hypertension, BMI, HDLC, TG) was 0.24, 95 %CI 0.08-0.7, p < 0.01 for GSTT1 null and 1.13, 95 %CI 0.62-2.07, p = 0.7 for GSTM1 null genotype. We found significantly lower plasma lipoprotein (a) (Lp(a)) levels in GSTT1 null compared to wild-type genotype carriers in patient group (20.68 ± 26.02 mg/dl vs. 40.66 ± 42.89 mg/dl, mean ± SD, p = 0.04). The serum interleukin-6 (IL-6) values were significantly influenced by both GST polymorphisms in patients with CP. Our results, showing the significant reduction of GSTT1 deletions in patients with CP, suggest involvement of GSTs in carotid atherosclerosis. This study shows additional view of the possible role of GSTs in advanced chronic inflammatory disease of vascular system, but the confirmation in a larger studies in different populations are needed.
谷胱甘肽S-转移酶（GSTs）在细胞中发挥着广泛的功能，如对内源性化合物进行解毒、清除活性氧，甚至催化解毒以外的代谢途径中的反应。基于先前的研究，GSTM1和GSTT1可能会改变动脉粥样硬化的风险。我们研究的目的是分析346例接受动脉内膜切除术的晚期动脉粥样硬化患者中，GSTM1和GSTT1基因多态性与颈动脉斑块（CP）发生的可能关联，以及氧化应激、血脂谱和炎症的生化参数。采用多重聚合酶链反应（PCR）方法检测346例患者和330例对照的基因组DNA中GSTM1和GSTT1基因的缺失情况。CP存在的校正OR值（校正年龄、性别、吸烟、高血压、BMI、HDLC、TG）对于GSTT1缺失型为0.24，95%CI为0.08 - 0.7，p < 0.01；对于GSTM缺失型基因型为1.13，95%CI为0.62 - 2.07，p = 0.7。我们发现患者组中，与野生型基因型携带者相比，GSTT1缺失型患者的血浆脂蛋白（a）（Lp(a)）水平显著降低（20.68±26.02mg/dl vs. 40.66±42.89mg/dl，均值±标准差，p = 0.04）。CP患者的血清白细胞介素-6（IL-6）值受两种GST多态性的显著影响。我们的结果显示CP患者中GSTT1缺失显著减少，提示GSTs参与颈动脉粥样硬化。本研究显示了GSTs在血管系统晚期慢性炎症性疾病中可能作用的新观点，但需要在不同人群中进行更大规模研究予以证实。
