Men, genes, and heart disease

Each week, we select an article from an influential journal that has broad implications for healthcare and has just become available for free online.

For a long time, we have known that men have a higher incidence of coronary artery disease than women of the same age. This is serious stuff, of course, since coronary artery disease can lead to heart attacks and strokes. Is it something in our genes? This study says yes.

The authors focused on the Y chromosome, the one that determines male sex. On the Y chromosome, they found a specific grouping of genes that is associated strongly with the development of coronary artery disease. Moreover, in working through the function of this group of genes, they learned that the genes affect immunity and inflammation. The latter observation ties in with current thinking that inflammation of blood vessel walls is often the key culprit in triggering heart attacks, which is scientifically satisfying.

Like all genetic studies, this one won’t influence clinical care in the near future. Eventually, if it’s possible to develop a reasonably-priced diagnostic test for this gene grouping, it could help to identify men at higher risk for coronary artery disease and influence how aggressively patients take preventive measures.

Check out the abstract below or go right to the free full text.

PubMed Citation:

Lancet. 2012 Mar 10;379(9819):915-22. Epub 2012 Feb 9.

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

Charchar FJ, Bloomer LD, Barnes TA, Cowley MJ, Nelson CP, Wang Y, Denniff M, Debiec R, Christofidou P, Nankervis S, Dominiczak AF, Bani-Mustafa A, Balmforth AJ, Hall AS, Erdmann J, Cambien F, Deloukas P, Hengstenberg C, Packard C, Schunkert H, Ouwehand WH, Ford I, Goodall AH, Jobling MA, Samani NJ, Tomaszewski M.

Source

School of Health Sciences, University of Ballarat, Ballarat, VIC, Australia.

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 chromosome 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.

FUNDING:

British Heart Foundation; UK National Institute for Health Research; LEW Carty Charitable Fund; National Health and Medical Research Council of Australia; European Union 6th Framework Programme; Wellcome Trust.

Copyright © 2012 Elsevier Ltd. All rights reserved.

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