Inheritance of coronary artery disease in men: an analysis of the role of the Y chromosome

被引：181

作者：

Charchar, Fadi J. ^{[2
]}

Bloomer, Lisa D. S. ^{[1
]}

Barnes, Timothy A. ^{[1
]}

Cowley, Mark J. ^{[4
]}

Nelson, Christopher P. ^{[1
,18
]}

Wang, Yanzhong ^{[5
]}

Denniff, Matthew ^{[1
]}

Debiec, Radoslaw ^{[1
]}

Christofidou, Paraskevi ^{[1
]}

Nankervis, Scott ^{[2
]}

Dominiczak, Anna F. ^{[6
]}

Bani-Mustafa, Ahmed ^{[2
]}

Balmforth, Anthony J. ^{[10
]}

Hall, Alistair S. ^{[10
]}

Erdmann, Jeanette ^{[11
]}

Cambien, Francois ^{[12
,13
]}

Deloukas, Panos ^{[14
]}

Hengstenberg, Christian ^{[15
]}

Packard, Chris ^{[8
,9
]}

Schunkert, Heribert

Ouwehand, Willem H. ^{[14
,16
,17
]}

Ford, Ian ^{[7
]}

Goodall, Alison H. ^{[1
,18
]}

Jobling, Mark A. ^{[3
]}

Samani, Nilesh J. ^{[1
,18
]}

Tomaszewski, Maciej ^{[1
,18
]}

机构：

[1] Univ Leicester, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England

[2] Univ Ballarat, Sch Hlth Sci, Ballarat, Vic 3353, Australia

[3] Univ Leicester, Dept Genet, Leicester LE3 9QP, Leics, England

[4] Garvan Inst Med Res, Wills Bioinformat Ctr, Sydney, NSW, Australia

[5] Kings Coll London, Div Hlth & Social Care Res, London WC2R 2LS, England

[6] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland

[7] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland

[8] Univ Glasgow, Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland

[9] Univ Glasgow, Dept Vasc Biochem, Glasgow, Lanark, Scotland

[10] Univ Leeds, Div Epidemiol, LIGHT, Sch Med, Leeds LS2 9JT, W Yorkshire, England

[11] Med Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany

[12] Univ Paris 06, INSERM, UMRS 937, Paris, France

[13] Sch Med, Paris, France

[14] Wellcome Trust Sanger Inst, Cambridge, England

[15] Univ Regensburg, Poliklin Innere Med 2, Regensburg, Germany

[16] Univ Cambridge, Dept Haematol, Cambridge, England

[17] Natl Hlth Serv Blood & Transplant, Cambridge, England

[18] Glenfield Gen Hosp, Natl Inst Hlth Res, Biomed Res Unit, Leicester LE3 9QP, Leics, England

来源：

LANCET | 2012年 / 379卷 / 9819期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

BLOOD-PRESSURE; LEUKOCYTE RECRUITMENT; ASSOCIATION ANALYSIS; HAPLOGROUP-I; ATHEROSCLEROSIS; MORTALITY; RISK;

D O I：

10.1016/S0140-6736(11)61453-0

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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.

引用

页码：915 / 922

页数：8

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