Research Article Molecular analysis of the GSTT1 gene polymorphism in patients with clinical manifestation of atherosclerosis.

Abstract

ABSTRACT. Atherosclerosis is a chronic inflammatory disease formed by the accumulation of lipids in the innermost layer and large-caliber artery (tunica intima). This accumulation, along with platelet factors, stimulates the proliferation of muscle cells in this region. Over than 400 genes may be related to the pathology since they regulate endothelial function, coagulation, inflammation, metabolism of amino acids, lipids, and carbohydrates. Glutathione S-transferases (GST) are enzymes that catalyze the polymorphic detoxification of metabolites produced by oxidative stress within the cells, which is induced by reactive oxygen species. GSTs are one of the defense mechanisms against oxidative stress damage. Due to genetic, cultural, and environmental factors, the rate of atherosclerosis is higher; however, an early diagnosis is crucial for the prevention and treatment of several complications related to the disease. The present study aimed to analyze the frequency of GSTT1 genotypes regarding the presence or absence of the polymorphism in patients with clinical manifestation of atherosclerosis. We collected 200 samples of peripheral blood of patients with the previous diagnosis of atherosclerosis based on clinical examination and imaging, and 100 samples of peripheral blood to compose the control group of patients without clinical manifestation of atherosclerosis. The polymorphism was assessed by PCR and analyzed on the agarose gel stained with 2.0% ethidium bromide. The frequency of the GSTT1 gene polymorphism was compared using the chi-square test (P < 0.05) and the G-test. In the case group, we detected 85.5% of patients with the GSTT1 genotype present and 14.5% of patients with the null genotype. A significant difference was observed between groups (case vs control) for the presence of the GSTT1 polymorphism. According to the analysis of the variable alcohol consumption, we found that in the case group the presence of the GSTT1 gene was higher in individuals who reported not drinking alcohol. In this study, the presence of the GSTT1 gene polymorphism in male patients with atherosclerosis was 1.5 times higher when compared to female patients. Regarding the variable time of smoking, we found that this genotype was more frequent in smokers for both case and control groups.

Association of Genetic Polymorphisms in GSTP1, GSTM1, and GSTT1 Genes with Vesicoureteral Reflux Susceptibility in the Children of Southeast Iran

“…GSTs cellular detoxification activities involve in inflammatory processes, cellular differentiation and signaling pathways ( 35 – 37 ). Studies performed in past years have revealed that oxidative stress worsens diseases caused by inflammatory response ( 38 , 39 ). Studies demonstrated GSTs enzyme activities always depend on their genotype.…”

The multifaceted role of genetic polymorphisms in atherosclerosis

“…Null mutations in GSTM1 have been associated with a large variety of diseases and an increased susceptibility to toxins [39,73]. Null mutations in GSTM1 increases the susceptibility diseases as well [40,75]. The GSTM1 present genotype was identified in a higher frequency in the Brazilian [39], Turkish [79] and British [80] population.…”

“…They catalyze the reduced form of glutathione into xenobiotic substrates, turning such compounds more water-soluble in order to fulfill their function of detoxification [72]. GSTs polymorphisms are linked to innumerous diseases and anomalies such cancer [73], drug resistance [74], diabetes [75], atherosclerosis [39,40], and other inflammatory [76] and autoimmune diseases [77,78].…”

“…GSTT1 present genotype has been found to be more frequent in certain populations from Brazil [40,81], India [82] and Serbia [83]. Interistingly, a study conducted in a Turkish population has shown that GSTT1 null genotype was nine-fold more frequent in atherosclerotic patients compared to healthy ones [79].…”

“…Hundreds of genes have been reported to be related to atherosclerosis and they regulated a myriad of physiological processes, including macromolecules metabolism, coagulation, detoxification, endothelial function and coagulation. Several of those genes are polymorphic and variations in their sequence contribute to the molecular pathogenesis of the disease [37][38][39][40][41]. The inherited risk of atherosclerosis is increased in families with multiple affected members [42].…”