Genetic variation is the major determinant of individual differences in leukocyte endothelial adhesion.
<h4>Objective</h4>To determine the genetic contribution to leukocyte endothelial adhesion.<h4>Methods</h4>Leukocyte endothelial adhesion was assessed through a novel cell-based assay using human lymphoblastoid cell lines. A high-throughput screening method was developed to ev...
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2014
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oai:doaj.org-article:8ac2cae563834316b10ab997c85eba302021-11-18T08:33:12ZGenetic variation is the major determinant of individual differences in leukocyte endothelial adhesion.1932-620310.1371/journal.pone.0087883https://doaj.org/article/8ac2cae563834316b10ab997c85eba302014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24520339/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objective</h4>To determine the genetic contribution to leukocyte endothelial adhesion.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>There is a heritable component to leukocyte endothelial adhesion. Underlying genetic predisposition plays a significant role in inter-individual variability of leukocyte endothelial adhesion.Michael A GrassiVidhya RaoKathryn P WinklerWei ZhangJoseph D BogaardSiquan ChenBonnie LaCroixDivya LenkalaJalees RehmanAsrar B MalikNancy J CoxR Stephanie HuangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e87883 (2014) |
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Medicine R Science Q Michael A Grassi Vidhya Rao Kathryn P Winkler Wei Zhang Joseph D Bogaard Siquan Chen Bonnie LaCroix Divya Lenkala Jalees Rehman Asrar B Malik Nancy J Cox R Stephanie Huang Genetic variation is the major determinant of individual differences in leukocyte endothelial adhesion. |
| description |
<h4>Objective</h4>To determine the genetic contribution to leukocyte endothelial adhesion.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>There is a heritable component to leukocyte endothelial adhesion. Underlying genetic predisposition plays a significant role in inter-individual variability of leukocyte endothelial adhesion. |
| format |
article |
| author |
Michael A Grassi Vidhya Rao Kathryn P Winkler Wei Zhang Joseph D Bogaard Siquan Chen Bonnie LaCroix Divya Lenkala Jalees Rehman Asrar B Malik Nancy J Cox R Stephanie Huang |
| author_facet |
Michael A Grassi Vidhya Rao Kathryn P Winkler Wei Zhang Joseph D Bogaard Siquan Chen Bonnie LaCroix Divya Lenkala Jalees Rehman Asrar B Malik Nancy J Cox R Stephanie Huang |
| author_sort |
Michael A Grassi |
| title |
Genetic variation is the major determinant of individual differences in leukocyte endothelial adhesion. |
| title_short |
Genetic variation is the major determinant of individual differences in leukocyte endothelial adhesion. |
| title_full |
Genetic variation is the major determinant of individual differences in leukocyte endothelial adhesion. |
| title_fullStr |
Genetic variation is the major determinant of individual differences in leukocyte endothelial adhesion. |
| title_full_unstemmed |
Genetic variation is the major determinant of individual differences in leukocyte endothelial adhesion. |
| title_sort |
genetic variation is the major determinant of individual differences in leukocyte endothelial adhesion. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/8ac2cae563834316b10ab997c85eba30 |
| work_keys_str_mv |
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