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Circ Cardiovasc Genet. 2017 Aug;10(4):e001544. doi: 10.1161/CIRCGENETICS.116.001544.

Loss of Y Chromosome in Blood Is Associated With Major Cardiovascular Events During Follow-Up in Men After Carotid Endarterectomy.

Author information

1
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 of Manchester, United Kingdom (J.E., M.T.); Division of Medicine, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, United Kingdom (M.T.); Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht (F.W.A.); and Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, United Kingdom (F.W.A.).
2
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 of Manchester, United Kingdom (J.E., M.T.); Division of Medicine, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Centre, United Kingdom (M.T.); Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht (F.W.A.); and Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, United Kingdom (F.W.A.). h.m.denruijter-2@umcutrecht.nl.

Abstract

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; r2=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.

KEYWORDS:

atherosclerosis; cardiovascular diseases; cytokines; genetics; inflammation

PMID:
28768751
DOI:
10.1161/CIRCGENETICS.116.001544
[Indexed for MEDLINE]

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