Charchar, Fadi J. and Bloomer, Lisa D. S. and Barnes, Timothy A. and Cowley, Mark J. and Nelson, Christopher P. and Wang, Yanzhong and Denniff, Matthew and Debiec, Radoslaw and Christofidou, Paraskevi and Nankervis, Scott and Dominiczak, Anna F. and Bani-Mustafa, Ahmed and Balmforth, Anthony J. and Hall, Alistair S. and Erdmann, Jeanette and Cambien, Francois and Deloukas, Panos and Hengstenberg, Christian and Packard, Chris and Schunkert, Heribert and Ouwehand, Willem H. and Ford, Ian and Goodall, Alison H. and Jobling, Mark A. and Samani, Nilesh J. and Tomaszewski, Maciej (2012) Inheritance of coronary artery disease in men: an analysis of the role of the Y chromosome. LANCET, 379 (9819). pp. 915-922. ISSN 0140-6736,
Full text not available from this repository. (Request a copy)Abstract
Background A sexual dimorphism exists in the incidence and prevalence of coronary artery disease-men are more commonly affected than are age-matched women. We explored the role of the Y chromosome in coronary artery disease in the context of this sexual inequity. Methods We genotyped 11 markers of the male-specific region of the Y chromosome in 3233 biologically unrelated British men from three cohorts: the British Heart Foundation Family Heart Study (BHF-FHS), West of Scotland Coronary Prevention Study (WOSCOPS), and Cardiogenics Study. On the basis of this information, each Y chromosome was tracked back into one of 13 ancient lineages defined as haplogroups. We then examined associations between common Y chromosome haplogroups and the risk of coronary artery disease in cross-sectional BHF-FHS and prospective WOSCOPS. Finally, we undertook functional analysis of Y chromo some effects on monocyte and macrophage transcriptome in British men from the Cardiogenics Study. Findings Of nine haplogroups identified, two (R1b1b2 and I) accounted for roughly 90% of the Y chromosome variants among British men. Carriers of haplogroup I had about a 50% higher age-adjusted risk of coronary artery disease than did men with other Y chromosome lineages in BHF-FHS (odds ratio 1.75, 95% CI 1.20-2.54, p=0.004), WOSCOPS (1.45, 1.08-1.95, p=0.012), and joint analysis of both populations (1.56, 1.24-1.97, p=0.0002). The association between haplogroup I and increased risk of coronary artery disease was independent of traditional cardiovascular and socioeconomic risk factors. Analysis of macrophage transcriptome in the Cardiogenics Study revealed that 19 molecular pathways showing strong differential expression between men with haplogroup I and other lineages of the Y chromosome were interconnected by common genes related to inflammation and immunity, and that some of them have a strong relevance to atherosclerosis. Interpretation The human Y chromosome is associated with risk of coronary artery disease in men of European ancestry, possibly through interactions of immunity and inflammation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BLOOD-PRESSURE; LEUKOCYTE RECRUITMENT; ASSOCIATION ANALYSIS; GENERAL-POPULATION; HEART-DISEASE; HAPLOGROUP-I; ATHEROSCLEROSIS; RISK; INFLAMMATION; PERSPECTIVE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 May 2020 09:06 |
| Last Modified: | 18 May 2020 09:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19062 |
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