Loss of Y Chromosome in Blood Is Associated With Major Cardiovascular Events During Follow-Up in Men After Carotid Endarterectomy
Open accessAbstract
Background— Recent studies found an immune regulatory role for Y chromosome and a relationship between loss of Y chromosome (LOY) in blood cells and a higher risk of cancer and mortality. Given involvement of immune cells in atherosclerosis, we hypothesized that LOY is associated with the severity of atherosclerotic plaque characteristics and outcome in men undergoing carotid endarterectomy. Methods and Results— LOY was quantified in blood and plaque from raw intensity genotyping data in men within the Athero-Express biobank study. Plaques were dissected, and the culprit lesions used for histology and the measurement of inflammatory proteins. We tested LOY for association with (inflammatory) atherosclerotic plaque phenotypes and cytokines and assessed the association of LOY with secondary events during 3-year follow-up. Of 366 patients with carotid endarterectomy, 61 exhibited some degree of LOY in blood. LOY was also present in atherosclerotic plaque lesions (n=8/242, 3%). LOY in blood was negatively associated with age (β=−0.03/10 y; r 2 =0.07; P =1.6×10 –7 ) but not with cardiovascular disease severity at baseline. LOY in blood was associated with a larger atheroma size (odds ratio, 2.15; 95% confidence interval, 1.06–4.76; P =0.04); however, this association was not significant after correction for multiple testing. LOY was independently associated with secondary major cardiovascular events (hazard ratio=2.28; 95% confidence interval, 1.11–4.67; P =0.02) in blood when corrected for confounders. Conclusions— In this hypothesis-generating study, LOY in blood is independently associated with secondary major cardiovascular events in a severely atherosclerotic population. Our data could indicate that LOY affects secondary outcome via other mechanisms than inflammation in the atherosclerotic plaque.
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CHIP is associated with multiple adverse outcomes in epidemiological studies.
“Like several other well-described markers in blood cells, such as red cell distribution width 83, DNA methylation clocks 84, and loss of Y-chromosome 85, CHIP is associated with multiple adverse outcomes in epidemiological studies.”
From Clonal hematopoiesis in human aging and disease (2019) · cites this paper as [85]
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Smoking and Cardiovascular Disease
Meßner, B., & Bernhard, D. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.113.300156 · Cited by 1,148 · see citing works
Local proliferation dominates lesional macrophage accumulation in atherosclerosis
Robbins, C. S., Hilgendorf, I., Weber, G. F., Theurl, I., Iwamoto, Y., Figueiredo, J.-L., Gorbatov, R., Sukhova, G. K., Gerhardt, L. M. S., Smyth, D., et al. (2013) · Nature Medicine · doi:10.1038/nm.3258 · Cited by 1,041 · see citing works
Forsberg, L. A., Rasi, C., Malmqvist, N., Davies, H., Pasupulati, S., Pakalapati, G., Sandgren, J., de Ståhl, T. D., Zaghlool, A., Giedraitis, V., et al. (2014) · Nature Genetics · doi:10.1038/ng.2966 · Cited by 460 · see citing works
Mosaic Loss of Chromosome y in Blood Is Associated with Alzheimer Disease
Dumanski, J. P., Lambert, J.-C., Rasi, C., Giedraitis, V., Davies, H., Grenier-Boley, B., Lindgren, C. M., Campion, D., Dufouil, C., Pasquier, F., et al. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2016.05.014 · Cited by 266 · see citing works
Distribution of Human Chromosome Counts in Relation to Age
Jacobs, P. A., Brown, W. M. C., & Doll, R. (1961) · Nature · doi:10.1038/1911178a0 · Cited by 249 · see citing works
Verhoeven, B. A. N., Velema, E., Schoneveld, A. H., de Vries, J. P. M., de Bruin, P. C., Seldenrijk, C. A., de Kleijn, D. P. V., Busser, E., van der Graaf, Y., Mol, F., et al. (2004) · European Journal of Epidemiology · doi:10.1007/s10564-004-2304-6 · Cited by 245 · see citing works
Self-citationSmoking is associated with mosaic loss of chromosome Y
Dumanski, J. P., Rasi, C., Lönn, M., Davies, H., Ingelsson, M., Giedraitis, V., Lannfelt, L., Magnusson, P. K. E., Lindgren, C. M., Morris, A. P., et al. (2014) · Science · doi:10.1126/science.1262092 · Cited by 244 · see citing works
Mosaic loss of chromosome Y is associated with common variation near TCL1A
Zhou, W., Machiela, M. J., Freedman, N. D., Rothman, N., Malats, N., Dagnall, C. L., Caporaso, N. E., Teras, L. T., Gaudet, M. M., Gapstur, S. M., et al. (2016) · Nature Genetics · doi:10.1038/ng.3545 · Cited by 236 · see citing works
Inheritance of coronary artery disease in men: an analysis of the role of the Y chromosome
Charchar, F. J., Bloomer, L. D. S., Barnes, T. A., Cowley, M. J., Nelson, C. P., Wang, Y., Denniff, M. J., Dębiec, R., Christofidou, P., Nankervis, S. A., et al. (2012) · The Lancet · doi:10.1016/s0140-6736(11)61453-0 · Cited by 216 · see citing works
Self-citationMini-chromosomes derived from the human Y chromosome by telomere directed chromosome breakage.
Heller, R., Brown, K. E., Burgtorf, C., et al. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.14.7125 · Cited by 146 · see citing works
Case, L. K., Wall, E. H., Dragon, J. A., Saligrama, N., Krementsov, D. N., Moussawi, M., Zachary, J. F., Huber, S. A., Blankenhorn, E. P., & Teuscher, C. (2013) · Genome Research · doi:10.1101/gr.156703.113 · Cited by 146 · see citing works
Y chromosome loss in male patients with primary biliary cirrhosis
Lleò, A., Oertelt‐Prigione, S., Bianchi, I., Caliari, L., Finelli, P., Miozzo, M. R., Lazzari, R., Floreani, A., Donato, F., Colombo, M., et al. (2013) · Journal of Autoimmunity · doi:10.1016/j.jaut.2012.12.008 · Cited by 113 · see citing works
Loss of Y Chromosome in Peripheral Blood of Colorectal and Prostate Cancer Patients
Noveski, P., Madjunkova, S., Stefanovska, E. S., Matevska-Geshkovska, N., Kuzmanovska, M., Dimovski, A. J., & Plaseska‐Karanfilska, D. (2016) · PLoS ONE · doi:10.1371/journal.pone.0146264 · Cited by 100 · see citing works
Persani, L., Bonomi, M., Lleò, A., Pasini, S. M., Civardi, F., Bianchi, I., Campi, I., Finelli, P., Miozzo, M. R., Castronovo, C., et al. (2011) · Journal of Autoimmunity · doi:10.1016/j.jaut.2011.11.011 · Cited by 92 · see citing works
The Y Chromosome Effect on Blood Pressure in Two European Populations
Charchar, F. J., Tomaszewski, M., Padmanabhan, S., Łacka, B., Upton, M. N., Inglis, G. C., Anderson, N., McConnachie, A., Zukowska-Szczechowska, E., Grzeszczak, W., et al. (2002) · Hypertension · doi:10.1161/hy0202.103413 · Cited by 87 · see citing works
Self-citationBloomer, L. D. S., Nelson, C. P., Denniff, M. J., Christofidou, P., Dębiec, R., Thompson, J. R., Zukowska-Szczechowska, E., Samani, N. J., Charchar, F. J., & Tomaszewski, M. (2014) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2013.12.012 · Cited by 30 · see citing works
Self-citationvan der Laan, S. W., Asl, H. F., van den Borne, P., van Setten, J., van der Perk, M. E. M., van de Weg, S. M., Schoneveld, A. H., de Kleijn, D. P. V., Michoel, T., Björkegren, J., et al. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.01.018 · Cited by 28 · see citing works
Self-citationHurks, R., Hoefer, I. E., Vink, A., de Vries, J. P. P. M., Heijmen, R. H., Schoneveld, A. H., Kerver, M., Pasterkamp, G., & Moll, F. L. (2010) · European Surgical Research · doi:10.1159/000318160 · Cited by 17 · see citing works
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“Like several other welldescribed markers in blood cells, such as red cell distributionwidth (84), DNAmethylation clocks (85), and loss of Y chromosome (86), CHIP is associated with multiple adverse outcomes in epidemiological studies.”
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- Authors
- Haitjema, S., Kofink, D., van Setten, J., van der Laan, S. W., Schoneveld, A. H., Eales, J., Tomaszewski, M., de Jager, S. C. A., Pasterkamp, G., Asselbergs, F. W., & den Ruijter, H. M.
- Affiliations
- Manchester Academic Health Science Centre (GB)
- From the Laboratory of Experimental Cardiology, Division Heart and Lungs (S.H., J.v.S., S.W.v.d.L., A.H.S., S.C.A.d.J., G.P., H.M.d.R.), Department of Medical Genetics, Center of Molecular Medicine (D.K.), Laboratory of Clinical Chemistry and Haematology, Division Laboratories and Pharmacy (G.P.), and Department of Cardiology, Division Heart and Lungs (F.W.A.), University Medical Center Utrecht, The Netherlands; Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University...
- ORCID
- Venue
- Circulation Cardiovascular Genetics
- Published
- 2017-08
- Volume
- 10
- Issue
- 4
- Pages
- e001544-e001544
- ISSN
- 1942-325X (ISSN-L)
- 1942-3268
- OpenAlex
- W2740242149
- Cited by
- 123
- References
- 18
- Citations by year
- 2026: 11 · 2025: 19 · 2024: 20 · 2023: 20 · 2022: 12 · 2021: 14 · 2020: 11 · 2019: 12 · 2018: 3 · 2017: 1
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Circulation Cardiovascular Genetics (publishedVersion)
- PubMed (publishedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Funders
- NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research
- National Institute for Health and Care Research
- British Heart Foundation (PG/16/49/32176, PG/12/9/29376)
- University College London
- European Commission (601456)
- Netherlands Heart Institute
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cerebrovascular and Carotid Artery Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Keywords
- Y chromosome loss, carotid endarterectomy, atherosclerotic plaque, secondary cardiovascular events, immune regulation, men, inflammatory cytokines, atherosclerosis, Y chromosome
- MeSH terms
- Aged, Carotid Arteries, Follow-Up Studies, Genotype, Humans, Male, Middle Aged, Smoking, Cohort Studies, Proportional Hazards Models, Odds Ratio, Endarterectomy, Carotid, Chromosomes, Human, Y, Atherosclerosis, Plaque, Atherosclerotic, Real-Time Polymerase Chain Reaction
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