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Tag Variants of LGALS-3 Containing Haplotype Block in Advanced Carotid Atherosclerosis

  • Ana Djordjevic
    Correspondence
    Corresponding author.
    Affiliations
    Department of Radiobiology and Molecular Genetics, “Vinca” Institute of Nuclear Sciences-National Institute of the Republic of Serbia, Mike Petrovica Alasa 12-14, P.O. Box 522, University of Belgrade, Belgrade 11001, Serbia
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  • Maja Zivkovic
    Affiliations
    Department of Radiobiology and Molecular Genetics, “Vinca” Institute of Nuclear Sciences-National Institute of the Republic of Serbia, Mike Petrovica Alasa 12-14, P.O. Box 522, University of Belgrade, Belgrade 11001, Serbia
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  • Igor Koncar
    Affiliations
    Clinic for Vascular and Endovascular Surgery, Clinical Center of Serbia, Belgrade, Serbia

    Medical Faculty, University of Belgrade, Belgrade, Serbia
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  • Aleksandra Stankovic
    Affiliations
    Department of Radiobiology and Molecular Genetics, “Vinca” Institute of Nuclear Sciences-National Institute of the Republic of Serbia, Mike Petrovica Alasa 12-14, P.O. Box 522, University of Belgrade, Belgrade 11001, Serbia
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  • Jovana Kuveljic
    Affiliations
    Department of Radiobiology and Molecular Genetics, “Vinca” Institute of Nuclear Sciences-National Institute of the Republic of Serbia, Mike Petrovica Alasa 12-14, P.O. Box 522, University of Belgrade, Belgrade 11001, Serbia
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  • Tamara Djuric
    Affiliations
    Department of Radiobiology and Molecular Genetics, “Vinca” Institute of Nuclear Sciences-National Institute of the Republic of Serbia, Mike Petrovica Alasa 12-14, P.O. Box 522, University of Belgrade, Belgrade 11001, Serbia
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      Abstract

      Objectives

      Galectin-3 affects a variety of biological processes. It is encoded by LGALS-3, located in unique haplotype block in Caucasians. Most of the studies regarding the gal-3 role in atherosclerosis are focused exclusively on protein/mRNA levels. Genetic analyses of LGALS-3 are scarce. We sought to thoroughly examine the genetic background of gal-3 and to analyze tag variants that cover more than 80% variability of the LGALS-3 containing hap-block in association with carotid plaque presence (CPP). According to Tagger server, rs4040064 G/T, rs11628437 G/A and rs7159490 C/T cover 82% (r2 > 0.8) of the genetic variance of this hap-block. Our aims were to investigate possible association of rs4040064, rs11628437 and rs7159490 haplotypes with CPP in patients with advanced carotid atherosclerosis (CA) and to analyze their possible effect on LGALS-3 mRNA expression in carotid plaques.

      Materials and methods

      Study group consisted of 468 patients and 296 controls. Rs4040064, rs11628437, rs7159490 and LGALS-3 mRNA expression were detected by TaqMan® technology.

      Results

      We have found that haplotype TAC was associated with the cerebrovascular insult (CVI) occurrence (OR = 1.68, 95% CI = 1.09-2.58, p = 0.02), compared to the referent haplotype. OR was adjusted for hypertension, age and BMI. TAC also showed higher, but not statistically significant, LGALS-3 expression in carotid plaques.

      Conclusions

      Our results suggest that rs4040064, rs11628437 and rs7159490 bear no association with CPP, neither they affect LGALS-3 mRNA in carotid plaques. However, we showed a significant association of haplotype TAC with the CVI occurrence in CA patients from Serbia. Replication and validation of our results are required.

      Key Words

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