title: Genetic variation is the major determinant of individual differences in leukocyte endothelial adhesion.
abstract: OBJECTIVE
  To determine the genetic contribution to leukocyte endothelial adhesion.
  
  
  METHODS
  Leukocyte endothelial adhesion was assessed through a novel cell-based assay using human lymphoblastoid cell lines. A high-throughput screening method was developed to evaluate the inter-individual variability in leukocyte endothelial adhesion using lymphoblastoid cell lines derived from different donors. To assess heritability, ninety-two lymphoblastoid cell lines derived from twenty-three monozygotic twin pairs and twenty-three sibling pairs were compared. These lymphoblastoid cell lines were plated with the endothelial cell line EA.hy926 and labeled with Calcein AM dye. Fluorescence was assessed to determine endothelial cell adhesion to each lymphoblastoid cell line. Intra-pair similarity was determined for monozygotic twins and siblings using Pearson pairwise correlation coefficients.
  
  
  RESULTS
  A leukocyte endothelial adhesion assay for lymphoblastoid cell lines was developed and optimized (CV = 8.68, Z'-factor = 0.67, SNR = 18.41). A higher adhesion correlation was found between the twins than that between the siblings. Intra-pair similarity for leukocyte endothelial adhesion in monozygotic twins was 0.60 compared to 0.25 in the siblings. The extent to which these differences are attributable to underlying genetic factors was quantified and the heritability of leukocyte endothelial adhesion was calculated to be 69.66% (p-value<0.0001).
  
  
  CONCLUSIONS
  There is a heritable component to leukocyte endothelial adhesion. Underlying genetic predisposition plays a significant role in inter-individual variability of leukocyte endothelial adhesion.
authors: Department of Ophthalmology & Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors: Michael A
authors: MA
authors: Grassi
authors: Department of Ophthalmology & Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors: Vidhya
authors: V
authors: Rao
authors: Department of Ophthalmology & Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors: Kathryn P
authors: KP
authors: Winkler
authors: Department of Pediatrics, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors: Wei
authors: W
authors: Zhang
authors: Department of Ophthalmology & Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors: Joseph D
authors: JD
authors: Bogaard
authors: Cellular Screening Center, Institute for Genomics and Systems Biology, University of Chicago, Chicago, Illinois, United States of America.
authors: Siquan
authors: S
authors: Chen
authors: Section of Hematology/Oncology, University of Chicago, Chicago, Illinois, United States of America.
authors: Bonnie
authors: B
authors: LaCroix
authors: Section of Hematology/Oncology, University of Chicago, Chicago, Illinois, United States of America.
authors: Divya
authors: D
authors: Lenkala
authors: Department of Pharmacology, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors: Jalees
authors: J
authors: Rehman
authors: Department of Pharmacology, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors: Asrar B
authors: AB
authors: Malik
authors: Section of Genetic Medicine, University of Chicago, Chicago, Illinois, United States of America.
authors: Nancy J
authors: NJ
authors: Cox
authors: Section of Hematology/Oncology, University of Chicago, Chicago, Illinois, United States of America.
authors: R Stephanie
authors: RS
authors: Huang
mesh_terms: D002448:Cell Adhesion; D002452:Cell Count; D002460:Cell Line; D015986:Confounding Factors, Epidemiologic; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D014644:Genetic Variation; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D007962:Leukocytes / Q000166:cytology* / Q000378:metabolism*; D015203:Reproducibility of Results; D035781:Siblings; D014430:Twins, Monozygotic / Q000235:genetics