Skip to main content
SpringerLink
Log in

Association of E-Selectin Gene Polymorphism and Serum PAPP-A with Carotid Atherosclerosis in End-Stage Renal Disease

  • Original Research Article
  • Published:
Molecular Diagnosis & Therapy Aims and scope Submit manuscript

Abstract

Background

Atherosclerotic vascular disease represents a significant cause of morbidity and mortality in patients with end-stage renal disease (ESRD). The endothelium plays a crucial role in vascular inflammation. E-selectin is exclusively expressed on activated endothelial cells and is upregulated following an inflammatory response and oxidative stress, while serum pregnancy-associated plasma protein-A (PAPP-A) concentrations are related to the presence and stability of carotid atherosclerotic plaques.

Objective

The aim of this study was to investigate whether there is an association between SELE rs5355C>T gene polymorphism, serum PAPP-A level and the presence of carotid atherosclerosis in ESRD patients.

Subjects and Methods

Seventy subjects were recruited into this study; 40 ESRD patients [age (mean ± SD) 43.42 ± 13.94 years] and 30 age- and gender-matched healthy individuals assigned to the control group. Polymerase chain reaction–restriction fragment length polymorphism was performed for the analysis of SELE rs5355C>T gene polymorphism, while serum PAPP-A concentrations were measured using electro-chemiluminescence immunoassay. Routine laboratory tests were measured on an automated chemistry analyzer. Carotid ultrasonographic studies were performed by a bilateral high-resolution B-mode ultrasound.

Results

There was no significant relationship between the SELE rs5355C>T gene polymorphism and ESRD incidence. Serum PAPP-A levels were significantly higher in ESRD patients compared with controls [median (interquartile range) 5.8 (5.1–11.6) and 5.1 (4.1–6.7), respectively; p = 0.005]. Serum PAPP-A correlated positively with urea, creatinine, systolic and diastolic blood pressure (DBP). Serum PAPP-A showed a statistically significant increase in SELE rs5355TT versus CC in both patients and controls. There was no association on comparing right intima-media thickness (IMT), left IMT, right cross-sectional area (CSA) and left CSA with the CC, CT and TT genotypes of SELE rs5355C>T. No correlation between serum PAPP-A with each of the above-mentioned carotid doppler findings was observed. There was a statistically significant increase in DBP in TT genotype carriers when compared with CC genotype carriers (p = 0.009). Serum PAPP-A levels were higher in hypertensive ESRD patients when compared with normotensive ESRD patients. There was a statistically significant decrease in high-density lipoprotein cholesterol (HDL-C) in TT genotype carriers when compared with CT genotype carriers in the whole study group (p = 0.003). Serum PAPP-A correlated negatively with HDL-C.

Conclusion

The lack of a direct association between SELE rs5355C>T gene polymorphism, serum PAPP-A level and IMT suggests that their hypothesized association with carotid atherosclerosis might reflect an indirect mechanism of SELE rs5355C>T gene polymorphism and serum PAPP-A with cardiovascular risk factors such as blood pressure and HDL-C rather than a direct effect on the vasculature.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Foley R, Parfrey P, Sarnak M. Clinical epidemiology of cardiovascular disease in chronic renal failure. Am J Kidney Dis. 1998;32:S112–9.

    Article  CAS  PubMed  Google Scholar 

  2. Herzog CA, Asinger RW, Berger AK, et al. Cardiovascular disease in chronic kidney disease. A clinical update from kidney disease: improving global outcomes (KDIGO). Kidney Int. 2011;80(6):572–86. doi:10.1038/ki.2011.223.

    Google Scholar 

  3. Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999;340:115–26.

    Article  CAS  PubMed  Google Scholar 

  4. Lawrence MB, Springer TA. Neutrophils roll on E-selectin. J Immunol. 1993;151:6338–46.

    CAS  PubMed  Google Scholar 

  5. Roldan V, Marin F, Lip GY, et al. Soluble E-selectin in cardiovascular disease and its risk factors: a review of the literature. Thromb Haemost. 2003;90:1007–20.

    CAS  PubMed  Google Scholar 

  6. Khazen D, Jendoubi-Ayed S, Aleya WB, et al. Polymorphism in ICAM-1, PECAM-1, E-selectin, and L-selectin genes in Tunisian patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2009;21:167–75.

    Article  CAS  PubMed  Google Scholar 

  7. Malatino LS, Stancanelli1 B, Cataliotti A, et al. Circulating E-selectin as a risk marker in patients with end-stage renal disease. J Internal Med. 2007;262:479–87. doi:10.1111/j.1365-2796.2007.01841.x.

    Google Scholar 

  8. Ehret GB, O’Connor AA, Weder A, et al. Follow up of a major linkage peak on chromosome 1 reveals suggestive QTLs associated with essential hypertension: GenNet study. Eur J Hum Genet. 2009;17:1650–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Hunt SC, Ellison RC, Atwood LD, et al. Genome scans for blood pressure and hypertension: the National Heart, Lung, and Blood Institute Family Heart Study. Hypertension. 2002;40:1–6.

    Article  CAS  PubMed  Google Scholar 

  10. Marteau JB, Sass C, Pfister M, Lambert D, Noyer-Weidner M, Visvikis S. The Leu-554Phe polymorphism in the E-selectin gene is associated with blood pressure in overweight people. J Hypertens. 2004;22:305–11.

    Article  CAS  PubMed  Google Scholar 

  11. Wenzel K, Stahn R, Speer A, et al. Functional characterization of atherosclerosis-associated Ser-128Arg and Leu554Phe E-selectin mutations. Biol Chem. 1999;380:661–7.

    Article  CAS  PubMed  Google Scholar 

  12. Jilma B, Kovar FM, Hron G, et al. Homozygosity in the single nucleotide polymorphism Ser128Arg in the E-selectin gene associated with recurrent venous thromboembolism. Arch Intern Med. 2006;166(15):1655–9.

    Google Scholar 

  13. Ridker PM. Inflammation, atherosclerosis, and cardiovascular risk: an epidemiologic view. Blood Coagul Fibrinol. 1999;10 Suppl. 1:S9–12.

    Google Scholar 

  14. Conover CA, Harrington SC, Bale LK, et al. Surface association of pregnancy-associated plasma protein-A accounts for its colocalization with activated macrophages. Am J Physiol Heart Circ Physiol. 2007;292(2):H994–1000.

    Article  CAS  PubMed  Google Scholar 

  15. Bayes-Genis A, Conover CA, Schwartz RS. The insulin-like growth factor axis: a review of atherosclerosis and restenosis. Circ Res. 2000;86:125–30.

    Article  CAS  PubMed  Google Scholar 

  16. Bunn RC, Fowlkes JL. Insulin-like growth factor binding protein proteolysis. Trends Endocrinol Metab. 2003;14:176–81.

    Article  PubMed  Google Scholar 

  17. Tayebjee MH, Lip GY, MacFadyen RJ. Matrix metalloproteinases in coronary artery disease: clinical and therapeutic implications and pathological significance. Curr Med Chem. 2005;12:917–25.

    Article  CAS  PubMed  Google Scholar 

  18. Beaudeux JL, Burc L, Imbert-Bismut F, et al. Serum plasma pregnancy-associated protein A: a potential marker of echogenic carotid atherosclerotic plaques in asymptomatic hyperlipidemic subjects at high cardiovascular risk. Arteriosclerosis Thrombosis Vasc Biol. 2003;23:e7–10.

    Google Scholar 

  19. Conover CA, Harrington SC, Bale LK. Differential regulation of pregnancy associated plasma protein-A in human coronary artery endothelial cells and smooth muscle cells. Growth Horm IGF Res. 2008;18(3):213–20.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Miller SA, Dynes DD, Polesky F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucl Acids Res. 1988;16(3):1215.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Testa A, Benedetto FA, Spoto B, et al. The E-selectin gene polymorphism and carotid atherosclerosis in end-stage renal disease. Nephrol Dial Transpl. 2006;21:1921–6. doi:10.1093/ndt/gfl115.

    Article  CAS  Google Scholar 

  22. Benedetto FA, Mallamaci F, Tripepi G, et al. Prognostic value of ultrasonographic measurement of carotid intima media thickness in dialysis patients. J Am Soc Nephrol. 2001;12:2458–64.

    CAS  PubMed  Google Scholar 

  23. Zoccali C, Mallamaci F, Tripepi G. Inflammation and atherosclerosis in end-stage renal disease. Blood Purif. 2003;21:29–36.

    Article  CAS  PubMed  Google Scholar 

  24. Hajilooi M, Alizadeh A-HM, Ranjbar M, et al. E-selectin gene polymorphisms in Iranian chronic hepatitis B patients. Hepat Mon. 2007;7(4):211–6.

    Google Scholar 

  25. Pallaud C, Gueguen R, Sass C, et al. Genetic influences on lipid metabolism trait variability within the Stanislas cohort. J Lipid Res. 2001;42:1879–91.

    CAS  PubMed  Google Scholar 

  26. McLaren AJ, Marshall SE, Haldar NA, et al. Adhesion molecule polymorphisms in chronic renal allograft failure. Kidney Int. 1999;55:1977–82.

    Article  CAS  PubMed  Google Scholar 

  27. Weinstein J, de Souza-e-Silva U, Paulson JC. Purification of a Gal beta 1 to 4GlcNAc alpha 2 to 6 sialyltransferase and a Gal beta 1 to 3(4)GlcNAc alpha 2 to 3 sialyltransferase to homogeneity from rat liver. J Biol Chem. 1982;257:13835–44.

    CAS  PubMed  Google Scholar 

  28. Revelle BM, Scott D, Beck PJ. Single amino acid residues in the E- and P-selectin epidermal growth factor domains can determine carbohydrate binding specificity. J Biol Chem. 1996;271:16160–70.

    Article  CAS  PubMed  Google Scholar 

  29. Wenzel K, Ernst M, Rohde K, et al. DNA polymorphisms in adhesion molecule genes: a new risk factor for early atherosclerosis. Hum Genet. 1996;97:15–20.

    Article  CAS  PubMed  Google Scholar 

  30. Haidari M, Hajilooi M, Rafiei AR, et al. E-selectin genetic variation as a susceptibility factor for ischemic stroke. Cerebrovasc Dis. 2009;28:26–32. doi:10.1159/000215940.

    Article  CAS  PubMed  Google Scholar 

  31. Kalousová M, Sulková S, Fialová L, et al. Glycoxidation and inflammation in chronic haemodialysis patients. Nephrol Dial Transplant. 2003;18:2577–2581. doi:10.1093/ndt/gfg404

    Google Scholar 

  32. Fialová l, Kalousová M, Soukupová J, et al. Relationship of pregnancy-associated plasma protein-a to renal function and dialysis modalities. Kidney Blood Pressure Res. 2004;27:88–95. doi:10.1159/000076390.

  33. Coskun A, Bicik Z, Duran S, et al. Pregnancy-associated plasma protein A in dialysis patients. Clin Chem Lab Med. 2007;45(1):63–6.

    CAS  PubMed  Google Scholar 

  34. Etter C, Straub Y, Hersberger M, et al. Pregnancy-associated plasma protein-A is an independent short-time predictor of mortality in patients on maintenance haemodialysis. Eur Heart J. 2010;31:354–9. doi:10.1093/eurheartj/ehp429.

    Article  CAS  PubMed  Google Scholar 

  35. Simon A, Gariepy J, Chironi G, et al. Intima media thickness: a new tool for diagnosis and treatment of cardiovascular risk. J Hypertens. 2002;20:159–69. doi:10.1097/00004872-200202000-00001.

    Article  CAS  PubMed  Google Scholar 

  36. Głowińska-Olszewska B, Tołwińska J, Urban M. Relationship between endothelial dysfunction, carotid artery intima media thickness and circulating markers of vascular inflammation in obese hypertensive children and adolescents. J Pediatr Endocrinol Metab. 2007;20(10):1125–36.

    PubMed  Google Scholar 

  37. Rubio-Guerra AF, Vargas-Robles H, Serrano AM, et al. Correlation between the levels of circulating adhesion molecules and atherosclerosis in type-2 diabetic normotensive patients. Cell Adhesion Migr. 2009;3(4):369–72.

    Article  Google Scholar 

  38. Woelfle J, Roth CL, Wunsch R, et al. Pregnancy-associated plasma protein A in obese children: relationship to markers and risk factors of atherosclerosis and members of the IGF system. Eur J Endocrinol. 2011;165:613–622.

    Google Scholar 

  39. Aso Y, Okumura K, Wakabayashi S, et al. Elevated pregnancy-associated plasma protein-A in sera from type 2 diabetic patients with hypercholesterolemia: associations with carotid atherosclerosis and toe-brachial index. J Clin Endocrinol Metab. 2004;89:5713–7.

    Article  CAS  PubMed  Google Scholar 

  40. Pellitero S, Reverter JL, Granada ML, et al. Association of the IGF1/pregnancy-associated plasma protein-A system and adipocytokine levels with the presence and the morphology of carotid plaques in type 2 diabetes mellitus patients with stable glycaemic control. Eur J Endocrinol. 2009;160:925–32.

    Article  CAS  PubMed  Google Scholar 

  41. Mueller T, Dieplinger B, Poelz W, et al. Increased pregnancy-associated plasma protein-A as a marker for peripheral atherosclerosis: results from the Linz Peripheral Arterial Disease Study. Clin Chem. 2006;52:1096–2103.

    Article  CAS  PubMed  Google Scholar 

  42. Faruque MU, Chen G, Doumatey A, Huang H, et al. Association of ATP1B1, RGS5 and SELE polymorphisms with hypertension and blood pressure in African–Americans. J Hypertens. 2011;29(10):1906–12.

    Article  CAS  PubMed  Google Scholar 

  43. Sass C, Pallaud C, Zannad F, et al. Association between E-selectin Leu554Phe polymorphism and blood pressure in the Stanislas cohort. Arch Mal Coeur Vaiss. 2001;94(8):855–8.

    CAS  PubMed  Google Scholar 

  44. El Shamieh S, Ndiaye NC, Stathopoulou MG, Murray HA, Masson C, Lamont JV, Fitzgerald P, Benetos A, Visvikis-Siest S. Functional epistatic interaction between rs6046G>A in F7 and rs5355C>T in SELE modifies systolic blood pressure levels. PLoS One. 2012;7(7):e40777. doi:10.1371/journal.pone.0040777.

    Article  PubMed Central  PubMed  Google Scholar 

  45. Cosin-Sales J, Kaski JC, Christiansen M, et al. Relationship among PAPP-A levels, clinical characteristics, and coronary artery disease extent in patients with chronic stable angina pectoris. Eur Heart J. 2005;26:2093–8.

    Article  CAS  PubMed  Google Scholar 

  46. Matsumoto K, Miyake S, Yano M, et al. High serum concentrations of soluble E-selectin in patients with impaired glucose tolerance with hyperinsulinemia. Atherosclerosis. 2000;152:415–20.

    Article  CAS  PubMed  Google Scholar 

  47. Barter PJ. Inhibition of endothelial cell adhesion molecule expression by high density lipoproteins. Clin Exp Pharmacol Physiol. 1997;24:286–7.

    Article  CAS  PubMed  Google Scholar 

  48. Calabresi L, Gomaraschi M, Villa B, et al. Elevated soluble cellular adhesion molecules in subjects with low HDL-cholesterol. Arterioscler Thromb Vasc Biol. 2002;22:656–61. doi:10.1161/hq0402.105901.

    Article  CAS  PubMed  Google Scholar 

  49. Torres MR, Sanjuliani AF. Effects of weight loss from a high-calcium energy-reduced diet on biomarkers of inflammatory stress, fibrinolysis, and endothelial function in obese subjects. Nutrition. 2013;29(1):143–51. doi:10.1016/j.nut.2012.05.012.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements and Disclosures

The preparation of this manuscript was not supported by any external funding. The authors have no conflicts of interest that are directly relevant to the content of this article.

Author information

Authors and Affiliations

  1. Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, El Saray St., El Manial, Cairo, 11956, Egypt

    Marianne Samir M. Issac, Alaa Afif, Nadida A. Gohar & Nahla A. Fawzy Fayek

  2. Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt

    Bahaa Zayed & Heba Sedrak

  3. Department of Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt

    Lamiaa Adel Salah El Din

Authors
  1. Marianne Samir M. Issac
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alaa Afif
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nadida A. Gohar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nahla A. Fawzy Fayek
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bahaa Zayed
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Heba Sedrak
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lamiaa Adel Salah El Din
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marianne Samir M. Issac.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 25 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Issac, M.S.M., Afif, A., Gohar, N.A. et al. Association of E-Selectin Gene Polymorphism and Serum PAPP-A with Carotid Atherosclerosis in End-Stage Renal Disease. Mol Diagn Ther 18, 243–252 (2014). https://doi.org/10.1007/s40291-013-0061-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40291-013-0061-4

Keywords

Search

Navigation