title: Effects of glutathione S-transferase T1 and M1 deletions on advanced carotid atherosclerosis, oxidative, lipid and inflammatory parameters.
abstract: 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.
authors.affiliation: Institute of Nuclear Sciences "VINCA", Laboratory for Radiobiology and Molecular Genetics -080, University of Belgrade, P.O. Box 522, 11000, Belgrade, Serbia, majaz@vinca.rs.
authors.forename: Maja
authors.initials: M
authors.lastname: Zivković
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Stanković
authors.forename: Tamara
authors.initials: T
authors.lastname: Djurić
authors.forename: Igor
authors.initials: I
authors.lastname: Končar
authors.forename: Ana
authors.initials: A
authors.lastname: Kolaković
authors.forename: Vladimir
authors.initials: V
authors.lastname: Djurdjević
authors.forename: Lazar
authors.initials: L
authors.lastname: Davidović
authors.forename: Dragan
authors.initials: D
authors.lastname: Alavantić
mesh_terms: D000368:Aged; D002340:Carotid Artery Diseases / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D015850:Interleukin-6 / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics; D011110:Polymorphism, Genetic; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors; D017384:Sequence Deletion
chemical_list: D005982:Glutathione Transferase; D015850:Interleukin-6; D017382:Reactive Oxygen Species; C413545:glutathione S-transferase T1