Male-Specific Region of the Y Chromosome and Cardiovascular Risk: Phylogenetic Analysis and Gene Expression Studies
Abstract
Objective—: Haplogroup I of male-specific region of the human Y chromosome is associated with 50% increased risk of coronary artery disease. It is not clear to what extent conventional cardiovascular risk factors and genes of the male-specific region may explain this association. Approach and Results—: A total of 1988 biologically unrelated men from 4 white European populations were genotyped using 11 Y chromosome single nucleotide polymorphisms and classified into 13 most common European haplogroups. Approximately 75% to 93% of the haplotypic variation of the Y chromosome in all cohorts was attributable to I, R1a, and R1b1b2 lineages. None of traditional cardiovascular risk factors, including body mass index, blood pressures, lipids, glucose, C-reactive protein, creatinine, and insulin resistance, was associated with haplogroup I of the Y chromosome in the joint inverse variance meta-analysis. Fourteen of 15 ubiquitous single-copy genes of the male-specific region were expressed in human macrophages. When compared with men with other haplogroups, carriers of haplogroup I had ≈0.61- and 0.64-fold lower expression of ubiquitously transcribed tetratricopeptide repeat, Y-linked gene ( UTY ) and protein kinase, Y-linked, pseudogene ( PRKY ) in macrophages ( P =0.0001 and P =0.002, respectively). Conclusions—: Coronary artery disease predisposing haplogroup I of the Y chromosome is associated with downregulation of UTY and PRKY genes in macrophages but not with conventional cardiovascular risk factors.
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PRKY is a pseudogene that has been associated with coronary artery disease in men carrying haplogroup I.
“It is a pseudogene that has been associated with coronary artery disease in men carrying haplogroup I 63 .”
From Sex-specific gene expression signatures of calcific aortic valve stenosis in a large collection of human tissues (2026) · cites this paper as [63]
The Discussion (p. 5) classifies PRKY as a transcribed pseudogene and reports an association between its expression and CAD-predisposing haplogroup I. The Significance section (p. 7) says PRKY is downregulated in macrophages from haplogroup I carriers, but leaves its contribution to CAD risk for future studies. The paper does not establish a direct association between PRKY and CAD in those men. (LLM, conf=0.86)
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Cites
Inference of Population Structure Using Multilocus Genotype Data
Pritchard, J. K., Stephens, M., & Donnelly, P. (2000) · Genetics · doi:10.1093/genetics/155.2.945 · Cited by 33,871 · see citing works
genalex 6: genetic analysis in Excel. Population genetic software for teaching and research
Peakall, R., & Smouse, P. E. (2005) · Molecular Ecology Notes · doi:10.1111/j.1471-8286.2005.01155.x · Cited by 16,596 · see citing works
The pathogenesis of atherosclerosis: a perspective for the 1990s
Ross, R. (1993) · Nature · doi:10.1038/362801a0 · Cited by 10,618 · see citing works
Falush, D., Stephens, M., & Pritchard, J. K. (2003) · Genetics · doi:10.1093/genetics/164.4.1567 · Cited by 7,920 · see citing works
Inferring weak population structure with the assistance of sample group information
HUBISZ, M. J., FALUSH, D., STEPHENS, M., & PRITCHARD, J. K. (2009) · Molecular Ecology Resources · doi:10.1111/j.1755-0998.2009.02591.x · Cited by 3,475 · see citing works
Inference of population structure using multilocus genotype data: dominant markers and null alleles
Falush, D., Stephens, M., & Pritchard, J. K. (2007) · Molecular Ecology Notes · doi:10.1111/j.1471-8286.2007.01758.x · Cited by 3,468 · see citing works
Yusuf, S., Hawken, S., Ôunpuu, S., Bautista, L., Franzosi, M. G., Commerford, P., Lang, C. C., Rumboldt, Z., Onen, C. L., Lisheng, L., et al. (2005) · The Lancet · doi:10.1016/s0140-6736(05)67663-5 · Cited by 2,903 · see citing works
The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes
Skaletsky, H., Kuroda-Kawaguchi, T., Minx, P. J., Cordum, H. S., Hillier, L., Brown, L. G., Repping, S., Pyntikova, T., Ali, J., Bieri, T. A., et al. (2003) · Nature · doi:10.1038/nature01722 · Cited by 2,098 · see citing works
Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
Cardiogenics, Schunkert, H., the CARDIoGRAM Consortium, König, I. R., Kathiresan, S., Reilly, M. P., Assimes, T. L., Holm, H., Preuss, M., Stewart, A. F. R., et al. (2011) · Nature Genetics · doi:10.1038/ng.784 · Cited by 1,866 · see citing works
Self-citationSarwar, N., Danesh, J., Eiriksdottir, G., Sigurdsson, G., Wareham, N., Bingham, S., Boekholdt, S. M., Khaw, K.-T., & Gudnason, V. (2007) · Circulation · doi:10.1161/circulationaha.106.637793 · Cited by 1,408 · see citing works
McQueen, M. J., Hawken, S., Wang, X., Ounpuu, S., Sniderman, A., Probstfield, J., Steyn, K., Sanderson, J. E., Hasani, M., Volkova, E., et al. (2008) · The Lancet · doi:10.1016/s0140-6736(08)61076-4 · Cited by 864 · see citing works
New binary polymorphisms reshape and increase resolution of the human Y chromosomal haplogroup treePreprint
Karafet, T. M., Mendez, F. L., Meilerman, M. B., Underhill, P. A., Zegura, S. L., & Hammer, M. F. (2008) · Genome Research · doi:10.1101/gr.7172008 · Cited by 854 · see citing works
A Nomenclature System for the Tree of Human Y-Chromosomal Binary HaplogroupsPreprint
The Y Chromosome Consortium (2002) · Genome Research · doi:10.1101/gr.217602 · Cited by 795 · see citing works
Psaty, B. M., Furberg, C. D., Kuller, L. H., Cushman, M., Savage, P. J., Levine, D. M., O’Leary, D. H., Bryan, R. N., Anderson, M. L., & Lumley, T. (2001) · Archives of Internal Medicine · doi:10.1001/archinte.161.9.1183 · Cited by 428 · see citing works
Ridker, P. M. (2004) · American Heart Journal · doi:10.1016/j.ahj.2004.04.028 · Cited by 290 · see citing works
Hallan, S. I., Astor, B., Romundstad, S., Aasarød, K., Kvenild, K., & Coresh, J. (2007) · PubMed · doi:10.1001/archinte.167.22.2490 · Cited by 284 · see citing works
A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk
Cardiogenics Consortium, Heinig, M., Petretto, E., Wallace, C., Bottolo, L., Rotival, M., Lu, H., Li, Y., Sarwar, R., Langley, S. R., et al. (2010) · Nature · doi:10.1038/nature09386 · Cited by 283 · see citing works
Self-citationDi Angelantonio, E., Chowdhury, R., Sarwar, N., Aspelund, T., Danesh, J., & Gudnason, V. (2010) · BMJ · doi:10.1136/bmj.c4986 · Cited by 275 · see citing works
Glomerular hyperfiltration: A new marker of metabolic risk
Tomaszewski, M., Charchar, F. J., Maric, C., McClure, J., Crawford, L., Grzeszczak, W., Sattar, N. A., Zukowska-Szczechowska, E., & Dominiczak, A. F. (2007) · Kidney International · doi:10.1038/sj.ki.5002160 · Cited by 234 · see citing works
Self-citationInsulin resistance and coronary heart disease in nondiabetic individuals
Reaven, G. (2012) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.111.241885 · Cited by 227 · 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-citationSarwar, N., Aspelund, T., Eiriksdottir, G., Gobin, R., Seshasai, S. R. K., Forouhi, N. G., Sigurdsson, G., Danesh, J., & Gudnason, V. (2010) · PLoS Medicine · doi:10.1371/journal.pmed.1000278 · Cited by 175 · see citing works
The Human UTY Gene Encodes a Novel HLA-B8-Restricted H-Y Antigen
Warren, E. H., Gavin, M. A., Simpson, E., Chandler, P., Page, D. C., Distèche, C. M., Stankey, K. A., Greenberg, P. D., & Riddell, S. R. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.5.2807 · Cited by 174 · see citing works
What's in a name? Y chromosomes, surnames and the genetic genealogy revolution
King, T. E., & Jobling, M. A. (2009) · Trends in Genetics · doi:10.1016/j.tig.2009.06.003 · Cited by 173 · see citing works
Vogt, M. H. J., Goulmy, E., Kloosterboer, F. M., Blokland, E. C., de Paus, R. A., Willemze, R., & Falkenburg, J. H. F. (2000) · Blood · doi:10.1182/blood.v96.9.3126 · Cited by 149 · 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-citationAssociation of the Human Y Chromosome With High Blood Pressure in the General Population
Ellis, J. A., Stebbing, M. S., & Harrap, S. B. (2000) · Hypertension · doi:10.1161/01.hyp.36.5.731 · Cited by 78 · see citing works
Association of the Human Y Chromosome with Cholesterol Levels in the General Population
Charchar, F. J., Tomaszewski, M., Łacka, B., Zakrzewski, J., Zukowska-Szczechowska, E., Grzeszczak, W., & Dominiczak, A. F. (2003) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000113291.39267.0a · Cited by 75 · see citing works
Self-citationGenetic Architecture of Ambulatory Blood Pressure in the General Population
Tomaszewski, M., Dębiec, R., Braund, P. S., Nelson, C. P., Hardwick, R. J., Christofidou, P., Denniff, M. J., Codd, V., Rafelt, S. E., van der Harst, P., et al. (2010) · Hypertension · doi:10.1161/hypertensionaha.110.155721 · Cited by 71 · see citing works
Self-citationLi, X., Li, H.-P., Amsler, K., Hyink, D. P., Wilson, P. D., & Burrow, C. R. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.132051799 · Cited by 58 · see citing works
C-reactive protein is a bystander of cardiovascular disease
Anand, S. S., & Yusuf, S. (2010) · European Heart Journal · doi:10.1093/eurheartj/ehq242 · Cited by 56 · see citing works
Y is there a risk to being male?
Charchar, F. J., Tomaszewski, M., Strahorn, P., Champagne, B., & Dominiczak, A. F. (2003) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(03)00032-8 · Cited by 49 · see citing works
Self-citationAssociation of Y chromosome haplogroup I with HIV progression, and HAART outcome
Sezgın, E., Lind, J. M., Shrestha, S., Hendrickson, S. L., Goedert, J. J., Donfield, S. M., Kirk, G. D., Phair, J., Troyer, J. L., O’Brien, S. J., et al. (2009) · Human Genetics · doi:10.1007/s00439-008-0620-7 · Cited by 36 · see citing works
Smad6 is a protein kinase X phosphorylation substrate and is required for HL-60 cell differentiation
Glesne, D. A., & Huberman, E. (2006) · Oncogene · doi:10.1038/sj.onc.1209436 · Cited by 30 · see citing works
Strahorn, P., Graham, D., Charchar, F. J., Sattar, N. A., McBride, M., & Dominiczak, A. F. (2005) · Journal of Hypertension · doi:10.1097/01.hjh.0000191904.26853.b8 · Cited by 28 · see citing works
Self-citationC-Reactive Protein and Cardiovascular Risk in the Framingham Study
Ridker, P. M., Rifai, N., Köenig, W., & Blumenthal, R. S. (2006) · Archives of Internal Medicine · doi:10.1001/archinte.166.12.1327-b · Cited by 14 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [27]27. Vogt MH, Goulmy E, Kloosterboer FM, Blokland E, de Paus RA, Willemze R, Falkenburg JH. UTY gene codes for an HLA-B60-restricted hu i niy noi -ir naem cell graft rejection: characterization of the critical polymorphic amino acid residues for T-cell recognition. Blood. 2000;96:3126–3132.
Cited by
Sorted by citations
Human UTY(KDM6C) Is a Male-specific Nϵ-Methyl Lysyl Demethylase
Walport, L. J., Hopkinson, R. J., Vollmar, M., Madden, S. K., Gileadi, C., Oppermann, U. C. T., Schofield, C. J., & Johansson, C. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.555052 · Cited by 220 · see citing works
“risk of male cardiovascular disease(24).”
Twentieth century surge of excess adult male mortality
Beltrán‐Sánchez, H., Finch, C. E., & Crimmins, E. M. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1421942112 · Cited by 179 · see citing works
“Could differing gene–environment interactions by sex contribute to the excess CVD male mortality? Some Y-chromosome haplotypes with CVD associations (40) also alter the expression of immune-related genes in macrophages (41).”
BackgroundThe Roles of Jumonji-Type Oxygenases in Human Disease
Johansson, C., Tumber, A., Che, K., Cain, P., Nowak, R. P., Gileadi, C., & Oppermann, U. C. T. (2014) · Epigenomics · doi:10.2217/epi.13.79 · Cited by 163 · see citing works
The Y chromosome: a blueprint for men’s health?
Maan, A., Eales, J., Akbarov, A., Rowland, J., Xu, X., Jobling, M. A., Charchar, F. J., & Tomaszewski, M. (2017) · European Journal of Human Genetics · doi:10.1038/ejhg.2017.128 · Cited by 165 · see citing works
Self-citationErrors in RNA-Seq quantification affect genes of relevance to human disease
Robert, C., & Watson, M. (2015) · Genome biology · doi:10.1186/s13059-015-0734-x · Cited by 153 · see citing works
“Haplogroup I [28] — a common European lineage of the Y chromosome — is known to be associated with an increased risk of coronary artery disease [29].”
BackgroundWhy are sex and gender important to basic physiology and translational and individualized medicine?
Miller, V. (2014) · American Journal of Physiology. Heart and Circulatory Physiology · doi:10.1152/ajpheart.00994.2013 · Cited by 150 · see citing works
Riemer, F., Kuehner, K. A., Ritz, S., Sauter‐Louis, C., & Hartmann, K. (2015) · Journal of Feline Medicine and Surgery · doi:10.1177/1098612x15586209 · Cited by 150 · see citing works
Genetics of cardiovascular disease: Importance of sex and ethnicity
Winham, S. J., de Andrade, M., & Miller, V. M. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.03.021 · Cited by 131 · see citing works
“Inflammation—The Y chromosome also includes genes involved with macrophage activation affecting innate immunity [50, 51].”
BackgroundHartman, R. J. G., Owsiany, K. M., Ma, L., Koplev, S., Hao, K., Slenders, L., Civelek, M., Mokrý, M., Kovacic, J. C., Pasterkamp, G., et al. (2021) · Circulation · doi:10.1161/circulationaha.120.051231 · Cited by 125 · see citing works
Women-Specific Factors to Consider in Risk, Diagnosis and Treatment of Cardiovascular Disease
Harvey, R. E., Coffman, K. E., & Miller, V. M. (2015) · Women s Health · doi:10.2217/whe.14.64 · Cited by 124 · see citing works
Alsiraj, Y., Thatcher, S. E., Charnigo, R. J., Chen, K. C., Blalock, E. M., Daugherty, A., & Cassis, L. A. (2016) · Circulation · doi:10.1161/circulationaha.116.023789 · Cited by 85 · see citing works
Sex differences in disease: sex chromosome and immunity
Feng, Z., Liao, M., & Zhang, L. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05990-2 · Cited by 59 · see citing works
“Changes in gene expression in specific regions of the Y chromosome in macrophages lead to downregulation of KDM6C and PRKY genes [131].”
Khramtsova, E. A., Wilson, M. A., Martin, J., Winham, S. J., He, K., Davis, L. K., & Stranger, B. E. (2023) · Cell · doi:10.1016/j.cell.2023.04.014 · Cited by 52 · see citing works
Statin therapy: does sex matter?
Faubion, S. S., Kapoor, E., Moyer, A. M., Hodis, H. N., & Miller, V. M. (2019) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000001412 · Cited by 55 · see citing works
“Immunological activation differs between males and females with a potential genetic contribution to predisposition to atherosclerosis associated with immune activation regulated by genes on the Y chromosome.(23,24) Current prescribing guidelines for statin therapy for primary and secondary prevention of cardiovascular…”
BackgroundHuman Y Chromosome Exerts Pleiotropic Effects on Susceptibility to Atherosclerosis
Eales, J., Maan, A., Xu, X., Michoel, T., Hallast, P., Batini, C., Zadik, D., Prestes, P. R., Molina, E., Denniff, M. J., et al. (2019) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.312405 · Cited by 54 · see citing works
Self-citationConsequences of Y chromosome microdeletions beyond male infertility
Colaco, S., & Modi, D. N. (2019) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-019-01492-z · Cited by 48 · see citing works
Y genetic variation and phenotypic diversity in health and disease
Case, L. K., & Teuscher, C. (2015) · Biology of Sex Differences · doi:10.1186/s13293-015-0024-z · Cited by 45 · see citing works
“Furthermore, macrophages from haplogroup I showed downregulation in the expression of the ChrY genes UTY and PRKY [47], suggesting that the”
BackgroundShould There Be Sex-Specific Criteria for the Diagnosis and Treatment of Heart Failure?
Greiten, L. E., Holditch, S. J., Arunachalam, S. P., & Miller, V. M. (2013) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-013-9514-8 · Cited by 42 · see citing works
“In men of European lineages, increased risk of myocardial infarction is also associated with variants on the male-specific region Y chromosome related to adaptive immunity [16].”
BackgroundChromosome Y genetic variants: impact in animal models and on human disease
Prokop, J. W., & Deschepper, C. F. (2015) · Physiological Genomics · doi:10.1152/physiolgenomics.00074.2015 · Cited by 39 · see citing works
“macrophages of men with MSY haplogroup I (which associates with increased risk of coronary artery disease) (13).”
BackgroundMolina, E., Chew, G. S., Myers, S., Clarence, E. M., Eales, J., Tomaszewski, M., & Charchar, F. J. (2017) · Scientific Reports · doi:10.1038/s41598-017-17165-9 · Cited by 37 · see citing works
Self-citationSexual Dimorphism of the Heart: Genetics, Epigenetics, and Development
Deegan, D. F., Nigam, P., & Engel, N. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.668252 · Cited by 36 · see citing works
Y Chromosome, Hypertension and Cardiovascular Disease: Is Inflammation the Answer?
Khan, S. I., Andrews, K. L., Jennings, G., Sampson, A. K., & Chin-Dusting, J. P. F. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20122892 · Cited by 33 · see citing works
“accumulating evidence in animals and humans suggests Y chromosome lineage may be one of the strongest genetic determinants of coronary artery disease to date [11].”
BackgroundBloomer, 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-citationIdentification of a Common Different Gene Expression Signature in Ischemic Cardiomyopathy
Li, Y., Qiu, J., Ding, Z., Liu, G., Yu, P., Jiang, G., Yu, Z., Yang, C., Qian, J., Jiang, H., et al. (2018) · Genes · doi:10.3390/genes9010056 · Cited by 23 · see citing works
“[43] showed that coronary artery disease-predisposing haplogroup I of chromosome Y was associated with the downregulation of UTY”
BackgroundClinical implications of Y chromosome microdeletions among infertile men
Punjani, N., Kang, C. L., & Schlegel, P. N. (2020) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2020.101471 · Cited by 22 · see citing works
Statins in High Cardiovascular Risk Patients: Do Comorbidities and Characteristics Matter?
Rossini, E., Biscetti, F., Rando, M. M., Nardella, E., Cecchini, A. L., Nicolazzi, M. A., Covino, M., Gasbarrini, A., Massetti, M., & Flex, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23169326 · Cited by 24 · see citing works
“Genetic variations in statin transporters and cytochromes lead to differential responses to statins and different side effects associated with myotoxicity [103,104].”
BackgroundY-chromosomal DNA analysis in French male lineages
Ramos‐Luis, E., Blanco‐Verea, A., Brión, M., Huffel, V. V., Sánchez‐Diz, P., & Carracedo, Á. (2014) · Forensic Science International Genetics · doi:10.1016/j.fsigen.2013.12.008 · Cited by 21 · see citing works
“Knowledge of the genetic structure of human populations is very important not only in historical studies [2,3], but also in medical [4–8], forensic [9–14], anthropological [15,16] and”
BackgroundProkop, J. W., Tsaih, S., Faber, A. B., Boehme, S., Underwood, A. C., Troyer, S., Playl, L. A., Milsted, A., Turner, M. E., Ely, D., et al. (2016) · Biology of Sex Differences · doi:10.1186/s13293-016-0064-z · Cited by 20 · see citing works
“MSY haplotypes in human correlate with increased risk of coronary artery disease and blood pressure [7, 8].”
BackgroundThe Y Chromosome: A Complex Locus for Genetic Analyses of Complex Human Traits
Parker, K., Erzurumluoglu, A. M., & Rodrı́guez, S. (2020) · Genes · doi:10.3390/genes11111273 · Cited by 20 · see citing works
Coronary Artery Disease: Why We should Consider the Y Chromosome
Molina, E., Clarence, E. M., Ahmady, F., Chew, G. S., & Charchar, F. J. (2016) · Heart Lung and Circulation · doi:10.1016/j.hlc.2015.12.100 · Cited by 19 · see citing works
Self-citationKolasa, A., Misiakiewicz-Has, K., Baranowska‐Bosiacka, I., Gutowska, I., & Wiszniewska, B. (2015) · Folia Histochemica et Cytobiologica · doi:10.5603/fhc.a2015.0025 · Cited by 19 · see citing works
O’Keeffe, L. M., Howe, L. D., Fraser, A., Hughes, A. D., Wade, K. H., Anderson, E. L., Lawlor, D. A., Erzurumluoglu, A. M., Smith, G. D., Rodrı́guez, S., et al. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.04.027 · Cited by 19 · see citing works
AZFa candidate gene UTY and its X homologue UTX are expressed in human germ cells
Vogt, P. H., Zimmer, J., Bender, U., & Strowitzki, T. (2021) · Reproduction and Fertility · doi:10.1530/raf-20-0049 · Cited by 18 · see citing works
Jun-ichi, S. U. T. O., & Satou, K. (2014) · BMC Research Notes · doi:10.1186/1756-0500-7-393 · Cited by 17 · see citing works
Y chromosome is moving out of sex determination shadow
Heydari, R., Jangravi, Z., Maleknia, S., Seresht‐Ahmadi, M., Bahari, Z., Salekdeh, G. H., & Meyfour, A. (2022) · Cell & Bioscience · doi:10.1186/s13578-021-00741-y · Cited by 17 · see citing works
“showed that the expression of UTY and PRKY decreased in macrophages derived from men with haplogroup I lineage [62].”
BackgroundPseudogenes in Cardiovascular Disease
Qi, Y., Wang, X., Li, W., Chen, D., Meng, H., & An, S. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2020.622540 · Cited by 16 · see citing works
Mechanisms of Sex Disparities in Cardiovascular Function and Remodeling
Chaudhari, S. K., Cushen, S. C., Osikoya, O., Jaini, P. A., Posey, R., Mathis, K. W., & Goulopoulou, S. (2018) · Comprehensive physiology · doi:10.1002/cphy.c180003 · Cited by 16 · see citing works
Sato, Y., Shinka, T., Nozawa, S., Yoshiike, M., Koh, E., Kanaya, J., Namiki, M., Matsumiya, K., Tsujimura, A., Komatsu, K., et al. (2015) · Andrology · doi:10.1111/andr.12026 · Cited by 15 · see citing works
“…chromosome haplogroup is also associated with several phenotypes other than male characteristics, including cardiovascular risk (Hiura et al., 2008; Bloomer et al., 2013; Kostrzewa et al., 2013), coronary artery disease (Charchar et al., 2012), lipids (Charchar et al., 2004; Russo et al., 2008),…”
BackgroundLamri, A., Paoli, M. D., de Souza, R. J., Werstuck, G. H., Anand, S. S., & Pigeyre, M. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.964743 · Cited by 13 · see citing works
Y Chromosome Genomic Variations and Biological Significance in Human Diseases and Health
Kuroki, Y., & Fukami, M. (2023) · Cytogenetic and Genome Research · doi:10.1159/000531933 · Cited by 13 · see citing works
Sex-limited chromosomes and non-reproductive traits
Cīrulis, A., Hansson, B., & Abbott, J. K. (2022) · BMC Biology · doi:10.1186/s12915-022-01357-5 · Cited by 12 · see citing works
Systems Biology and Noninvasive Imaging of Atherosclerosis
Calcagno, C., Mulder, W. J. M., Nahrendorf, M., & Fayad, Z. A. (2016) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.115.306350 · Cited by 13 · see citing works
“ciation between the haplogroup 1 of the Y male chromosome and an increased risk of CAD.(60) New studies at the interface between metabolomics (lipidomics) and proteomics have shed light on the complexity of the human lipoproteome,(64,65)”
BackgroundZhang, S., Niu, Q., Lin, T., Liu, S., Wang, P., Xu, H., Li, B., & Zhang, H. (2023) · BMC Genomics · doi:10.1186/s12864-023-09519-7 · Cited by 11 · see citing works
“The expression of UTY and PRKY was found associated with the risk of CAD [37, 38].”
BackgroundSex chromosomes and cardiovascular disease
Spiering, A. E., Groenheide, P. J., Mokrý, M., Onland‐Moret, N. C., Civelek, M., Reue, K., Benavente, E. D., & den Ruijter, H. M. (2025) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwaf224 · Cited by 12 · see citing works
Conversion of M1 Macrophages to Foam Cells: Transcriptome Differences Determined by Sex
Nambo‐Venegas, R., Palacios‐González, B., Mas‐Oliva, J., Aurioles-Amozurrutia, A. K., Cruz‐Rangel, A., Moreno, A., Hidalgo‐Miranda, A., Rodríguez‐Dorantes, M., Vadillo‐Ortega, F., Xicohtencatl‐Cortés, J., et al. (2023) · Biomedicines · doi:10.3390/biomedicines11020490 · Cited by 10 · see citing works
“The present study identifies several genes associated with the immune system, including CXCL3 and CXCL2, linked to immunoregulatory and inflammatory processes; IL-6, which codifies for a cytokine that regulates the inflammation process and maturation of B cells; INHBA, encoding for TGF-β (transforming growth factor-be…”
BackgroundKido, T., & Lau, Y. C. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.02.083 · Cited by 10 · see citing works
“Numerous studies have suggested that genes on the male specific Y-chromosome play a wide spectrum of functions, beside sex determination, and mutations of which contribute a variety of male-enhanced/restricted diseases, such as azoospermia [1], hearing loss [2], heart and cardiovascular diseases [3], testicular germ c…”
BackgroundSex‐dimorphic gene regulation in murine macrophages across niches
McGill, C. J., White, O. S., Lu, R. J., Sampathkumar, N. K., & Benayoun, B. A. (2025) · Immunology and Cell Biology · doi:10.1111/imcb.70030 · Cited by 8 · see citing works
Sex as a modifier of genetic risk for type 1 diabetes
Qu, H., & Hakonarson, H. H. (2025) · Diabetes Obesity and Metabolism · doi:10.1111/dom.70124 · Cited by 8 · see citing works
Pan‐risk factor for a comprehensive cardiovascular health management
Zheng, R., Xu, Y., Li, M., Lu, J., Xu, M., Wang, T., Zhao, Z., Wang, S., Lin, H., Zhang, X., et al. (2022) · Journal of Diabetes · doi:10.1111/1753-0407.13258 · Cited by 7 · see citing works
“The Y chromosome is one of the strongest genetic determinants of coronary artery disease (CAD).(9,10) Even in the presence of similar CVD risk factors for both men and women, compared with men, women suffer from CVD 7 to 10 years later, which has been largely ascribed to the protective effects of estrogen before menop…”
Backgroundde Haan, H. G., Vlieg, A. V. H., van der Gaag, K. J., de Knijff, P., & Rosendaal, F. R. (2016) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.13437 · Cited by 8 · see citing works
Using Y-Chromosomal Haplogroups in Genetic Association Studies and Suggested Implications
Erzurumluoglu, A. M., Baird, D. A., Richardson, T. G., Timpson, N. J., & Rodrı́guez, S. (2018) · Genes · doi:10.3390/genes9010045 · Cited by 8 · see citing works
“rarely been considered in the design and interpretation of genetic association studies although there are examples including direct testing of the association between Y-DNA haplogroups and phenotypes, including cardio-metabolic diseases [5-10].”
BackgroundHaitjema, S., van Setten, J., Eales, J., van der Laan, S. W., Gandin, I., de Vries, J. P. P. M., de Borst, G. J., Pasterkamp, G., Asselbergs, F. W., Charchar, F. J., et al. (2017) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2017.02.011 · Cited by 7 · see citing works
Self-citationAn Introduction to Epigenetics in Cardiovascular Development, Disease, and Sexualization
Cunningham, C. M., & Eghbali, M. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-77932-4_2 · Cited by 6 · see citing works
Association Between Size of Left Ventricle and Long‐Term Cardiovascular Events
Cheng, Y., Liao, Z., Liu, L., Ma, Y., Chen, X., Wu, Z., Wei, H., Lin, W., Liao, Y., Wu, S., et al. (2025) · Journal of the American Heart Association · doi:10.1161/jaha.124.040490 · Cited by 3 · see citing works
“30,31 Systemic inflammation, characterized by macrophage activation and elevated circulating cytokines, contributes to atherosclerosis development.”
The Y-Chromosome in Forensic and Public Health Genetics
Hall, T. O. (2016) · ResearchWorks at the University of Washington (University of Washington) · Cited by 3 · see citing works
Y chromosome and cardiovascular risk: What are we missing?
Voskarides, K. (2017) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2017.02.026 · Cited by 3 · see citing works
Chromosome-Y haplogroups in Asturias (Northern Spain) and their association with severe COVID-19
González-Fernández, M., Vázquez‐Coto, D., Albaiceta, G. M., Amado‐Rodríguez, L., Clemente, M. M. G., Velázquez-Cuervo, L., García-Lago, C., Gómez, J., & Coto, E. (2024) · Molecular Genetics and Genomics · doi:10.1007/s00438-024-02143-4 · Cited by 2 · see citing works
“…and men with this haplogroup presented changes in expression of genes involved in atherosclerosis, response to viral infection, lipid metabolism, coagulation and haemostasis (Charchar et al. 2012; Bloomer et al. 2013; Voskarides et al. 2014; Eales et al. 2019; Maan et al. 2017; Lorca et al. 2023).”
BackgroundHouessou, U., Zamani, P., Manikpurage, H. D., Li, Z., Gaudreault, N., Dahmene, M., Dagenais, F., Couture, C., Clavel, M.-A., Pibarot, P., et al. (2026) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2026.120791 · Cited by 1 · see citing works
Genetic Analysis of 27 Y-STR Haplotypes in 11 Iranian Ethnic Groups
Alinaghi, S., Mohseni, M., Fattahi, Z., Beheshtian, M., Ghodratpour, F., Ashrafi, F. Z., Arzhangi, S., Jalalvand, K., Najafipour, R., Khorshid, H. R. K., et al. (2024) · Archives of Iranian Medicine · doi:10.34172/aim.2024.13 · Cited by 1 · see citing works
“10,11 For example, the UTY and KDM5D genes modulate the inflammatory and adaptive immunity processes that contribute to atherosclerosis and the resulting outcomes of CVD. 2,12,13 Mutations in the SLY and RBMY genes impact experimental allergic encephalomyelitis (EAE) and experimental myocarditis.”
BackgroundBhass, S., & Banerjee, M. (2025) · Epigenomics · doi:10.1080/17501911.2025.2567232 · Cited by 1 · see citing works
An Overview of Sex and Gender in Pulmonary and Critical Care Medicine
Kay, S., & Pisani, M. A. (2021) · Clinics in Chest Medicine · doi:10.1016/j.ccm.2021.04.001 · Cited by 1 · see citing works
Sex and Gender Differences in Cardiovascular Disease
Mathews, L. M., Chandrashekar, P., Prasad, M., Miller, V. M., Sharma, K., Sedlak, T., Merz, C. N. B., & Ouyang, P. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809657-4.64153-4 · Cited by 1 · see citing works
No association between Y chromosomal haplogroups and severe acne in the Han Chinese population
Guo, M., Wu, W., Fan, L., Peng, M., Yang, J., Zhang, W., Hao, F., Xie, H., Xiang, L. F., Zheng, M., et al. (2014) · Journal of Human Genetics · doi:10.1038/jhg.2014.53
Genomic Landscape of Human Y Chromosome and Male Infertility
Singh, V., & Singh, K. (2017) · Springer eBooks · doi:10.1007/978-981-10-4017-7_6
OBSOLETE: Sex and Gender Differences in Cardiovascular Disease
Ouyang, P. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.64153-3
A Novel Deep Neural Networks Model Based on Prime Numbers for Y DNA Haplogroup Prediction
Dhaliwal, J., Keong, J., & Jin, Z. (2020) · IEEE Access · doi:10.1109/access.2020.3022274
Women in Cardiovascular Genetics and Systems Medicine
(2024) · Frontiers research topics · doi:10.3389/978-2-8325-4796-0
Sapozhnikov, M., Medina-Paz, F., Castagnola, M. J., & Zapico, S. C. (2024) · Forensic Sciences · doi:10.3390/forensicsci4040043
Mechanisms of Sex Disparities in Cardiovascular Function and Remodeling
Chaudhari, S. K., Cushen, S. C., Osikoya, O., Jaini, P. A., Posey, R., Mathis, K. W., & Goulopoulou, S. (2019) · Comprehensive physiology · doi:10.1002/j.2040-4603.2019.tb00059.x
Zhang, S., Niu, Q., Tong, L. X., Liu, S., Wang, P., Xu, H., Li, B., & Zhang, H. (2024) · Figshare · doi:10.6084/m9.figshare.26605522
Zhang, S., Niu, Q., Tong, L. X., Liu, S., Wang, P., Xu, H., Li, B., & Zhang, H. (2024) · Figshare · doi:10.6084/m9.figshare.26605525
Zhang, S., Niu, Q., Tong, L. X., Liu, S., Wang, P., Xu, H., Li, B., & Zhang, H. (2024) · Figshare · doi:10.6084/m9.figshare.26605507
Zhang, S., Niu, Q., Tong, L. X., Liu, S., Wang, P., Xu, H., Li, B., & Zhang, H. (2024) · Figshare · doi:10.6084/m9.figshare.26605519
Zhang, S., Niu, Q., Tong, L. X., Liu, S., Wang, P., Xu, H., Li, B., & Zhang, H. (2024) · Figshare · doi:10.6084/m9.figshare.26605510
Zhang, S., Niu, Q., Tong, L. X., Liu, S., Wang, P., Xu, H., Li, B., & Zhang, H. (2024) · Figshare · doi:10.6084/m9.figshare.26605504
Zhang, S., Niu, Q., Tong, L. X., Liu, S., Wang, P., Xu, H., Li, B., & Zhang, H. (2024) · Figshare · doi:10.6084/m9.figshare.26605516
Zhang, S., Niu, Q., Tong, L. X., Liu, S., Wang, P., Xu, H., Li, B., & Zhang, H. (2024) · Figshare · doi:10.6084/m9.figshare.26605534
Zhang, S., Niu, Q., Tong, L. X., Liu, S., Wang, P., Xu, H., Li, B., & Zhang, H. (2024) · Figshare · doi:10.6084/m9.figshare.26605531
Zhang, S., Niu, Q., Tong, L. X., Liu, S., Wang, P., Xu, H., Li, B., & Zhang, H. (2024) · Figshare · doi:10.6084/m9.figshare.26605513
Zhang, S., Niu, Q., Tong, L. X., Liu, S., Wang, P., Xu, H., Li, B., & Zhang, H. (2024) · Figshare · doi:10.6084/m9.figshare.26605528
Sex and Gender Differences in Cardiovascular Disease
Mehta, P. K., Mathews, L. M., Chandrashekar, P., Prasad, M., Miller, V. M., Sharma, K., Sedlak, T., Merz, C. N. B., Ouyang, P., & Vaccarino, V. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-15734-9.00085-6
BindingDB Entry 8054: Human UTY(KDM6C) is a male-specific Nϵ-methyl lysyl demethylase.
BindingDB (2017) · UC San Diego · doi:10.7270/q23x85j4
- Authors
- Bloomer, L. D. S., Nelson, C. P., Eales, J., Denniff, M., Christofidou, P., Debiec, R., Moore, J., Consortium, C., Zukowska-Szczechowska, E., Goodall, A. H., Thompson, J., Samani, N. J., Charchar, F. J., & Tomaszewski, M.
- Affiliations
- Federation University (AU)
- From the Department of Cardiovascular Sciences (L.D.S.B., C.P.N., J.E., M.D., P.C., R.D., J.M., A.H.G., N.J.S., F.J.C., M.T.) and Department of Health Sciences (J.T.), University of Leicester, Leicester, United Kingdom; Leicester National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, United Kingdom (C.P.N., A.H.G., J.T., N.J.S., M.T.); Department of Internal Medicine, Diabetology, and Nephrology, Medical University of Silesia, Zabrze...
- ORCID
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2013-07
- Volume
- 33
- Issue
- 7
- Pages
- 1722-1727
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W1970261618
- Cited by
- 75
- References
- 36
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 10 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 5 · 2018: 5 · 2017: 7 · 2016: 6 · 2015: 9 · 2014: 8 · 2013: 1
- FWCI
- 5.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- FedUni ResearchOnline (Federation University Australia) (submittedVersion)
- Funders
- University Hospitals of Leicester NHS Trust
- National Institute for Health and Care Research
- British Heart Foundation (PG/06/097/21331, PG/12/9/29376)
- European Commission (LSHM-CT 2006–037593)
- Medical Research Council
- National Health and Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Keywords
- Y chromosome, coronary artery disease, cardiovascular risk, Y-chromosome haplotypes, UTY, macrophages, gene expression, European men
- MeSH terms
- Adolescent, Adult, Cardiovascular Diseases, Europe, Gene Expression Regulation, Haplotypes, Humans, Macrophages, Male, Nuclear Proteins, Phenotype, Phylogeny, Pseudogenes, Risk Factors, Sex Factors, Biomarkers, Minor Histocompatibility Antigens, Linear Models, Odds Ratio, Protein Serine-Threonine Kinases, Risk Assessment, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Gene Expression Profiling, Chromosomes, Human, Y, White People, Young Adult, Arterial Pressure
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