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The sex-specific association of Met62Ile gene polymorphism in P-selectin glycoprotein ligand (PSGL-1) with carotid plaque presence: preliminary study

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Abstract

Atherosclerosis is known as an inflammatory disease in which a recruitment of leukocytes to the endothelium wall represents a preliminary step of the initiation and the development of disease. The P-selectin glycoprotein ligand (PSGL-1) seems to be the major molecule mediating leukocyte–endothelium interactions and leukocyte rolling on stimulated endothelium. There are limited number of studies reporting on association of Met62Ile SNP in PSGL-1 gene and the risk for atherosclerosis. The aim of this study was to analyze possible association of this polymorphism with an advanced carotid atherosclerosis and biochemical markers of inflammation and haemostasis. The 275 patients consecutively admitted for carotid endarterectomy with stenosis >70% and 256 controls of the same ethnic origin were included in the study. The Met62Ile genotypes were determined by PCR RFLP. The Ile/Ile homozygotes had significantly higher CRP compared to the other genotypes in patients. Female patients had Ile allele dose-dependent association with the carotid plaque presence (Met/Met vs. Met/Ile vs. Ile/Ile; OR 1, OR 2.02, CI 1.0–4.08, OR 4.08, CI 1.0–16.81, respectively, p = 0.04). Our results suggest the impact of PSGL-1 Met62Ile polymorphism on inflammation in advanced atherosclerosis. We observed the sex-differential association of Met62Ile with advanced carotid atherosclerosis. Studies in larger and different populations should validate and further examine the suggested role of genetic variations in PSGL-1 with atherosclerosis and thrombosis.

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References

  1. Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352:1685–1695

    Article  PubMed  CAS  Google Scholar 

  2. Moore KL, Stults NL, Diaz S, Smith DF, Cummings RD, Varki A, McEver RP (1992) Identification of a specific glycoprotein ligand for P-selectin (CD62) on myeloid cells. J Cell Biol 118:445–456

    Article  PubMed  CAS  Google Scholar 

  3. Moore KL, Patel KD, Bruehl RE, Li F, Johnson DA, Lichenstein HS, Cummings RD, Bainton DF, McEver RP (1995) P-selectin glycoprotein ligand-1 mediates rolling of human neutrophils on P-selectin. J Cell Biol 128:661–671

    Article  PubMed  CAS  Google Scholar 

  4. Laszik Z, Jansen PJ, Cummings RD, Tedder TF, McEver RP, Moore KL (1996) P-selectin glycoprotein ligand-1 is broadly expressed in cells of myeloid, lymphoid, and dendritic lineage and in some nonhematopoietic cells. Blood 88:3010–3021

    PubMed  CAS  Google Scholar 

  5. Norman KE, Katopodis AG, Thoma G, Kolbinger F, Hicks AE, Cotter MJ, Pockley AG, Hellewell PG (2000) P-selectin glycoprotein ligand-1 supports rolling on E- and P-selectin in vivo. Blood 96:3585–3591

    PubMed  CAS  Google Scholar 

  6. Norman KE, Moore KL, McEver RP, Ley K (1995) Leukocyte rolling in vivo is mediated by P-selectin glycoprotein ligand-1. Blood 86:4417–4421

    PubMed  CAS  Google Scholar 

  7. Frenette PS, Denis CV, Weiss L, Jurk K, Subbarao S, Kehrel B, Hartwig JH, Vestweber D, Wagner DD (2000) P-selectin glycoprotein ligand 1 (PSGL-1) is expressed on platelets and can mediate platelet–endothelial interactions in vivo. J Exp Med 191:1413–1422

    Article  PubMed  CAS  Google Scholar 

  8. Diacovo TG, Roth SJ, Buccola JM, Bainton DF, Springer TA (1996) Neutrophil rolling, arrest, and transmigration across activated, surface-adherent platelets via sequential action of P-selectin and the β2-integrin CD11b/CD18. Blood 1(146):157

    Google Scholar 

  9. Konstantopoulos K, Neelamegham S, Burns AR, Hentzen E, Kansas GS, Snapp KR, Berg EL, Hellums JD, Smith CW, McIntre LV, Simon SI (1998) Venous levels of shear support neutrophil–platelet adhesion and neutrophil aggregation in blood via P-selectin and β2-integrin. Circulation 98:873–882

    PubMed  CAS  Google Scholar 

  10. Sako D, Chang X-J, Barone KM, Vachino G, White HM, Shaw G, Veldman GM, Bean KM, Ahern TJ, Furie B, Cumming DA, Larsen GR (1993) Expression cloning of a functional glycoprotein ligand for P-selectin. Cell 75:1179–1186

    Article  PubMed  CAS  Google Scholar 

  11. Veldman GM, Bean KM, Cumming DA, Eddy RL, Sait SN, Shows TB (1995) Genomic organization and chromosomal localization of the gene encoding human P-selectin glycoprotein ligand. J Biol Chem 270:16470–16475

    Article  PubMed  CAS  Google Scholar 

  12. Tregouet DA, Barbaux S, Poirier O, Blankenberg S, Bickel C, Escolano S, Rupprecht HJ, Meyer J, Cambien F, Tiret L, AtheroGene Group (2003) SELPLG gene polymorphisms in relation to plasma SELPLG levels and coronary artery disease. Ann Hum Genet 67:504–511

    Article  PubMed  CAS  Google Scholar 

  13. Bugert P, Vosberg M, Entelmann M, Jahn J, Katus HA, Klüter H (2004) Polymorphisms in the P-selectin (CD62P) and P-selectin glycoprotein ligand-1 (PSGL-1) genes and coronary heart disease. Clin Chem Lab Med 42:997–1004

    Article  PubMed  CAS  Google Scholar 

  14. Roldán V, González-Conejero R, Marín F, Pineda J, Vicente V, Corral J (2004) Short alleles of P-selectin glycoprotein ligand-1 protect against premature myocardial infarction. Am Heart J 148:602–605

    Article  PubMed  Google Scholar 

  15. Ozben B, Diz-Kucukkaya R, Bilge AK, Hancer VS, Oncul A (2007) The association of P-selectin glycoprotein ligand-1 VNTR polymorphisms with coronary stent restenosis. J Thromb Thrombolysis 23:181–187

    Article  PubMed  CAS  Google Scholar 

  16. Volcik KA, Ballantyne CM, Coresh J, Folsom AR, Boerwinkle E (2007) Specific P-selectin and P-selectin glycoprotein ligand-1 genotypes/haplotypes are associated with risk of incident CHD and ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) study. Atherosclerosis 195:e76–e82

    Article  PubMed  CAS  Google Scholar 

  17. Wyman RA, Fraizer MC, Keevil JG, Busse KL, Aeschlimann SE, Korcarz CE, Stein JH (2005) Ultrasound-detected carotid plaque as a screening tool for advanced subclinical atherosclerosis. Am Heart J 150:1081–1085

    Article  PubMed  Google Scholar 

  18. European Carotid Surgery Trialists’ Collaborative Group (1991) MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70–99%) or with mild (0–29%) stenosis. Lancet 337:1235–1243

    Article  Google Scholar 

  19. Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502

    PubMed  CAS  Google Scholar 

  20. Kunkel LM, Smith KD, Boyer SH, Borgaonkar DS, Wachtel SS, Miller OJ, Breg WR, Jones HW Jr, Rary JM (1977) Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc Natl Acad Sci USA 74:1245–1249

    Article  PubMed  CAS  Google Scholar 

  21. Anderson JL, Carlquist JF, King GJ, Morrison L, Thomson MJ, Ludwig EH, Muhlestein JB, Bair TL, Ward RH (1998) Angiotensin-converting enzyme genotypes and risk for myocardial infarction in women. J Am Coll Cardiol 31:790–796

    Article  PubMed  CAS  Google Scholar 

  22. Stanković A, Zivković M, Alavantić D (2002) Angiotensin I-converting enzyme gene polymorphism in a Serbian population: a gender-specific association with hypertension. Scand J Clin Lab Invest 62:469–475

    Article  PubMed  Google Scholar 

  23. Petrovic D, Bregar D, Guzic-Salobir B, Skof E, Span M, Terzić R, Petrovic MG, Keber I, Letonja M, Zorc M, Podbregar M, Peterlin B (2004) Sex difference in the effect of ACE-DD genotype on the risk of premature myocardial infarction. Angiology 55:155–158

    Article  PubMed  Google Scholar 

  24. Pleskovič A, Vraspir-Porenta O, Zorc-Pleskovič R, Petrovič D, Zorc M, Milutinović A (2011) Deficiency of mast cells in coronary artery endarterectomy of male patients with type 2 diabetes. Cardiovasc Diabetol 10:40

    Article  PubMed  Google Scholar 

  25. Ober C, Loisel DA, Gilad Y (2008) Sex-specific genetic architecture of human disease. Nat Rev Genet 9:911–922

    Article  PubMed  CAS  Google Scholar 

  26. Liao YC, Lin HF, Guo YC, Yu ML, Liu CK, Juo SH (2010) Sex-differential genetic effect of phosphodiesterase 4D (PDE4D) on carotid atherosclerosis. BMC Med Genet 11:93

    Article  PubMed  Google Scholar 

  27. Wang L, Yanuck D, Beecham A, Gardener H, Slifer S, Blanton SH, Sacco RL, Rundek T (2011) A candidate gene study revealed sex-specific association between the OLR1 gene and carotid plaque. Stroke 42:588–592

    Article  PubMed  CAS  Google Scholar 

  28. Tuttle HA, Davis-Gorman G, Goldman S, Copeland JG, McDonagh PF (2003) Platelet–neutrophil conjugate formation is increased in diabetic women with cardiovascular disease. Cardiovasc Diabetol 2:12

    Article  PubMed  Google Scholar 

  29. Bazzoni G, Dejana E, Mashcio AD (1991) Platelet–neutrophil interactions. Possible relevance in the pathogenesis of thrombosis and inflammation. Haematologica 76:491–499

    PubMed  CAS  Google Scholar 

  30. Libby P, Ridker PM, Maseri A (2002) Inflammation and atherosclerosis. Circulation 105:1135–1143

    Article  PubMed  CAS  Google Scholar 

  31. Fischer JE, Bachman LM, Jaeschke R (2003) A readers’ guide to the interpretation of diagnostic test properties: clinical example of sepsis. Intensive Care Med 29:1043–1051

    Article  PubMed  Google Scholar 

  32. Hingorani AD, Shah T, Casas JP, Humphries SE, Talmud PJ (2009) C-reactive protein and coronary heart disease: predictive test or therapeutic target? Clin Chem 55:239–255

    Article  PubMed  CAS  Google Scholar 

  33. Vandendries ER, Furie BC, Furie B (2004) Role of P-selectin and PSGL-1 in coagulation and thrombosis. Thromb Haemost 92:459–466

    PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by Serbian Ministry of Education and Science Grants 175085 and 41028.

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Authors and Affiliations

  1. Laboratory for Radiobiology and Molecular Genetics, Institute of Nuclear Sciences “Vinča”, University of Belgrade, P.O. Box 522, 11001, Belgrade, Serbia

    Maja Živković, Ana Kolaković, Tamara Djurić & Aleksandra Stanković

  2. Vascular Surgery Clinic, Cardiovascular Institute Dedinje, Belgrade, Serbia

    Djordje Radak & Sandra Radak

  3. Clinic for Urgent Medicine, Military Medical Academy, Belgrade, Serbia

    Dragan Dinčić

Authors
  1. Maja Živković
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  2. Ana Kolaković
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  3. Djordje Radak
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  4. Dragan Dinčić
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  5. Sandra Radak
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  6. Tamara Djurić
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  7. Aleksandra Stanković
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Correspondence to Maja Živković.

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Živković, M., Kolaković, A., Radak, D. et al. The sex-specific association of Met62Ile gene polymorphism in P-selectin glycoprotein ligand (PSGL-1) with carotid plaque presence: preliminary study. Mol Biol Rep 39, 6479–6485 (2012). https://doi.org/10.1007/s11033-012-1475-5

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  • DOI: https://doi.org/10.1007/s11033-012-1475-5

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