title: Association of E-selectin gene polymorphism and serum PAPP-A with carotid atherosclerosis in end-stage renal disease.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, El Saray St., El Manial, Cairo, 11956, Egypt, mariannesamir@kasralainy.edu.eg.
authors.forename: Marianne Samir M
authors.initials: MS
authors.lastname: Issac
authors.forename: Alaa
authors.initials: A
authors.lastname: Afif
authors.forename: Nadida A
authors.initials: NA
authors.lastname: Gohar
authors.forename: Nahla A Fawzy
authors.initials: NA
authors.lastname: Fayek
authors.forename: Bahaa
authors.initials: B
authors.lastname: Zayed
authors.forename: Heba
authors.initials: H
authors.lastname: Sedrak
authors.forename: Lamiaa Adel
authors.initials: LA
authors.lastname: Salah El Din
mesh_terms: D000328:Adult; D002340:Carotid Artery Diseases / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019040:E-Selectin / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*
chemical_list: D019040:E-Selectin; C546936:SELE protein, human; D011266:Pregnancy-Associated Plasma Protein-A; C579283:PAPPA protein, human