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Genetic Variation Is the Major Determinant of Individual Differences in Leukocyte Endothelial Adhesion.

Authors :
Grassi, Michael A.
Rao, Vidhya
Winkler, Kathryn P.
Zhang, Wei
Bogaard, Joseph D.
Chen, Siquan
LaCroix, Bonnie
Lenkala, Divya
Rehman, Jalees
Malik, Asrar B.
Cox, Nancy J.
Huang, R. Stephanie
Source :
PLoS ONE; Feb2014, Vol. 9 Issue 2, p1-8, 8p
Publication Year :
2014

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
19326203
Volume :
9
Issue :
2
Database :
Complementary Index
Journal :
PLoS ONE
Publication Type :
Academic Journal
Accession number :
94729662
Full Text :
https://doi.org/10.1371/journal.pone.0087883