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Effects of glutathione S-transferase T1 and M1 deletions on advanced carotid atherosclerosis, oxidative, lipid and inflammatory parameters

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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.

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Acknowledgments

This work was supported by Serbian Government Research Grants (OI175085 and III41028).

Conflict of interest

All authors declare no conflict of interest.

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Authors and Affiliations

  1. Institute of Nuclear Sciences “VINCA”, Laboratory for Radiobiology and Molecular Genetics -080, University of Belgrade, P.O. Box 522, 11000, Belgrade, Serbia

    Maja Živković, Aleksandra Stanković, Tamara Djurić, Ana Kolaković, Vladimir Djurdjević & Dragan Alavantić

  2. Clinical Center of Serbia, Institute for Cardiovascular Diseases, University of Belgrade, Belgrade, Serbia

    Igor Končar & Lazar Davidović

Authors
  1. Maja Živković
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  2. Aleksandra Stanković
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  3. Tamara Djurić
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  4. Igor Končar
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  6. Vladimir Djurdjević
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Correspondence to Maja Živković.

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Živković, M., Stanković, A., Djurić, T. et al. Effects of glutathione S-transferase T1 and M1 deletions on advanced carotid atherosclerosis, oxidative, lipid and inflammatory parameters. Mol Biol Rep 41, 1157–1164 (2014). https://doi.org/10.1007/s11033-013-2962-z

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  • DOI: https://doi.org/10.1007/s11033-013-2962-z

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