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Antiphospholipid antibodies in a large population-based cohort: genome-wide associations and effects on monocyte gene expression

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Antiphospholipid antibodies in a large population-based cohort: genome-wide associations and effects on monocyte gene expression. / Müller-Calleja, Nadine; Rossmann, Heidi; Müller, Christian; Wild, Philipp; Blankenberg, Stefan; Pfeiffer, Norbert; Binder, Harald; Beutel, Manfred E; Manukyan, Davit; Zeller, Tanja; Lackner, Karl J.

In: THROMB HAEMOSTASIS, Vol. 116, No. 1, 04.07.2016, p. 115-123.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Müller-Calleja, N, Rossmann, H, Müller, C, Wild, P, Blankenberg, S, Pfeiffer, N, Binder, H, Beutel, ME, Manukyan, D, Zeller, T & Lackner, KJ 2016, 'Antiphospholipid antibodies in a large population-based cohort: genome-wide associations and effects on monocyte gene expression', THROMB HAEMOSTASIS, vol. 116, no. 1, pp. 115-123. https://doi.org/10.1160/TH15-12-0947

APA

Müller-Calleja, N., Rossmann, H., Müller, C., Wild, P., Blankenberg, S., Pfeiffer, N., Binder, H., Beutel, M. E., Manukyan, D., Zeller, T., & Lackner, K. J. (2016). Antiphospholipid antibodies in a large population-based cohort: genome-wide associations and effects on monocyte gene expression. THROMB HAEMOSTASIS, 116(1), 115-123. https://doi.org/10.1160/TH15-12-0947

Vancouver

Müller-Calleja N, Rossmann H, Müller C, Wild P, Blankenberg S, Pfeiffer N et al. Antiphospholipid antibodies in a large population-based cohort: genome-wide associations and effects on monocyte gene expression. THROMB HAEMOSTASIS. 2016 Jul 4;116(1):115-123. https://doi.org/10.1160/TH15-12-0947

Bibtex

@article{0c5ef9ad8c0340dea23a0c16a7a3fc94,
title = "Antiphospholipid antibodies in a large population-based cohort: genome-wide associations and effects on monocyte gene expression",
abstract = "The antiphospholipid syndrome (APS) is characterised by venous and/or arterial thrombosis and pregnancy morbidity in women combined with the persistent presence of antiphospholipid antibodies (aPL). We aimed to identify genetic factors associated with the presence of aPL in a population based cohort. Furthermore, we wanted to clarify if the presence of aPL affects gene expression in circulating monocytes. Titres of IgG and IgM against cardiolipin, β2glycoprotein 1 (anti-β2GPI), and IgG against domain 1 of β2GPI (anti-domain 1) were determined in approx. 5,000 individuals from the Gutenberg Health Study (GHS) a population based cohort of German descent. Genotyping was conducted on Affymetrix Genome-Wide Human SNP 6.0 arrays. Monocyte gene expression was determined in a subgroup of 1,279 individuals by using the Illumina HT-12 v3 BeadChip. Gene expression data were confirmed in vitro and ex vivo by qRT-PCR. Genome wide analysis revealed significant associations of anti-β2GPI IgG and APOH on chromosome 17, which had been previously identified by candidate gene approaches, and of anti-domain1 and MACROD2 on chromosome 20 which has been listed in a previous GWAS as a suggestive locus associated with the occurrence of anti-β2GPI antibodies. Expression analysis confirmed increased expression of TNFα in monocytes and identified and confirmed neuron navigator 3 (NAV3) as a novel gene induced by aPL. In conclusion, MACROD2 represents a novel genetic locus associated with aPL. Furthermore, we show that aPL induce the expression of NAV3 in monocytes and endothelial cells. This will stimulate further research into the role of these genes in the APS.",
keywords = "Adult, Aged, Antibodies, Antiphospholipid/blood, Antiphospholipid Syndrome/blood, Cohort Studies, Female, Gene Expression, Genome-Wide Association Study, Humans, Male, Membrane Proteins/genetics, Middle Aged, Monocytes/immunology, Nerve Tissue Proteins/genetics, Polymorphism, Single Nucleotide, Pregnancy, Prospective Studies, RNA/blood",
author = "Nadine M{\"u}ller-Calleja and Heidi Rossmann and Christian M{\"u}ller and Philipp Wild and Stefan Blankenberg and Norbert Pfeiffer and Harald Binder and Beutel, {Manfred E} and Davit Manukyan and Tanja Zeller and Lackner, {Karl J}",
year = "2016",
month = jul,
day = "4",
doi = "10.1160/TH15-12-0947",
language = "English",
volume = "116",
pages = "115--123",
journal = "THROMB HAEMOSTASIS",
issn = "0340-6245",
publisher = "Schattauer",
number = "1",

}

RIS

TY - JOUR

T1 - Antiphospholipid antibodies in a large population-based cohort: genome-wide associations and effects on monocyte gene expression

AU - Müller-Calleja, Nadine

AU - Rossmann, Heidi

AU - Müller, Christian

AU - Wild, Philipp

AU - Blankenberg, Stefan

AU - Pfeiffer, Norbert

AU - Binder, Harald

AU - Beutel, Manfred E

AU - Manukyan, Davit

AU - Zeller, Tanja

AU - Lackner, Karl J

PY - 2016/7/4

Y1 - 2016/7/4

N2 - The antiphospholipid syndrome (APS) is characterised by venous and/or arterial thrombosis and pregnancy morbidity in women combined with the persistent presence of antiphospholipid antibodies (aPL). We aimed to identify genetic factors associated with the presence of aPL in a population based cohort. Furthermore, we wanted to clarify if the presence of aPL affects gene expression in circulating monocytes. Titres of IgG and IgM against cardiolipin, β2glycoprotein 1 (anti-β2GPI), and IgG against domain 1 of β2GPI (anti-domain 1) were determined in approx. 5,000 individuals from the Gutenberg Health Study (GHS) a population based cohort of German descent. Genotyping was conducted on Affymetrix Genome-Wide Human SNP 6.0 arrays. Monocyte gene expression was determined in a subgroup of 1,279 individuals by using the Illumina HT-12 v3 BeadChip. Gene expression data were confirmed in vitro and ex vivo by qRT-PCR. Genome wide analysis revealed significant associations of anti-β2GPI IgG and APOH on chromosome 17, which had been previously identified by candidate gene approaches, and of anti-domain1 and MACROD2 on chromosome 20 which has been listed in a previous GWAS as a suggestive locus associated with the occurrence of anti-β2GPI antibodies. Expression analysis confirmed increased expression of TNFα in monocytes and identified and confirmed neuron navigator 3 (NAV3) as a novel gene induced by aPL. In conclusion, MACROD2 represents a novel genetic locus associated with aPL. Furthermore, we show that aPL induce the expression of NAV3 in monocytes and endothelial cells. This will stimulate further research into the role of these genes in the APS.

AB - The antiphospholipid syndrome (APS) is characterised by venous and/or arterial thrombosis and pregnancy morbidity in women combined with the persistent presence of antiphospholipid antibodies (aPL). We aimed to identify genetic factors associated with the presence of aPL in a population based cohort. Furthermore, we wanted to clarify if the presence of aPL affects gene expression in circulating monocytes. Titres of IgG and IgM against cardiolipin, β2glycoprotein 1 (anti-β2GPI), and IgG against domain 1 of β2GPI (anti-domain 1) were determined in approx. 5,000 individuals from the Gutenberg Health Study (GHS) a population based cohort of German descent. Genotyping was conducted on Affymetrix Genome-Wide Human SNP 6.0 arrays. Monocyte gene expression was determined in a subgroup of 1,279 individuals by using the Illumina HT-12 v3 BeadChip. Gene expression data were confirmed in vitro and ex vivo by qRT-PCR. Genome wide analysis revealed significant associations of anti-β2GPI IgG and APOH on chromosome 17, which had been previously identified by candidate gene approaches, and of anti-domain1 and MACROD2 on chromosome 20 which has been listed in a previous GWAS as a suggestive locus associated with the occurrence of anti-β2GPI antibodies. Expression analysis confirmed increased expression of TNFα in monocytes and identified and confirmed neuron navigator 3 (NAV3) as a novel gene induced by aPL. In conclusion, MACROD2 represents a novel genetic locus associated with aPL. Furthermore, we show that aPL induce the expression of NAV3 in monocytes and endothelial cells. This will stimulate further research into the role of these genes in the APS.

KW - Adult

KW - Aged

KW - Antibodies, Antiphospholipid/blood

KW - Antiphospholipid Syndrome/blood

KW - Cohort Studies

KW - Female

KW - Gene Expression

KW - Genome-Wide Association Study

KW - Humans

KW - Male

KW - Membrane Proteins/genetics

KW - Middle Aged

KW - Monocytes/immunology

KW - Nerve Tissue Proteins/genetics

KW - Polymorphism, Single Nucleotide

KW - Pregnancy

KW - Prospective Studies

KW - RNA/blood

U2 - 10.1160/TH15-12-0947

DO - 10.1160/TH15-12-0947

M3 - SCORING: Journal article

C2 - 27098658

VL - 116

SP - 115

EP - 123

JO - THROMB HAEMOSTASIS

JF - THROMB HAEMOSTASIS

SN - 0340-6245

IS - 1

ER -