By Oscar Millan-Iturbe MD / MPH
I found this fascinating article; hopefully all of you can review it in full text. Basically it is an investigation from European and Australian researchers whom give an explanation for why men have an increased risk of coronary artery disease compared with women. In their report published in the Lancet, the investigators conclude that a particular Y chromosome haplotype is associated with increased risk of CAD in men of European origin. They note that this association “might be mediated through a genetically programmed profile of immunity and response to inflammation.”
Dr. Fadi Charchar and colleagues performed a cross-sectional case–control analysis of 633 white, British men with no known history of CAD (controls) and 811 white, British men with a validated history of CAD and a strong family history of the condition. One Y chromosome haplotype, called ‘I’, was associated with a 75% increase in risk of CAD (age-adjusted OR 1.75, 95% CI 1.20–2.54, P = 0.004).
The association of haplotype I with the prospective development of CAD was confirmed (age-adjusted OR 1.45, 95% CI 1.08–1.95, P = 0.012) in a group of 1,534 Scottish men who had been involved in a clinical trial assessing statin-mediated primary prevention of CAD. No cardiovascular risk factors (including alcohol consumption, blood pressure, BMI, C-reactive protein level, diabetes mellitus, glucose level, lipid levels, or smoking status) or socioeconomic factors (such as education level and employment status) were associated with the haplotype. After combining the data from the two analyses, the researchers concluded that Y chromosome haplotype I increased risk of CAD by approximately 50%.
In subsequent analysis of the monocyte and macrophage transcriptomes, Charchar et al. found that 19 molecular pathways related to inflammation and immunity in the macrophage were altered in men with haplotype I compared with carriers of other haplotypes. By contrast, no changes in monocyte pathways were associated with haplotype I. The investigators speculate that this finding “suggests that differentiation (activation) of monocytes to macrophages, one of the key steps in the pathogenesis of atherosclerosis, might be the stage at which haplotype I exerts its molecular effects on CAD.”
Charchar, F. J. et al. Inheritance of coronary artery disease in men: an analysis of the role of the Y chromosome. Lancet doi: 10.1016/S0140-6736(11)61453-0