Abstract
The mechanisms underlying gender differences in stroke incidence, risk, and outcome are uncertain. We sought to determine whether transcriptional profiles of circulating blood cells of men and women differentially correlated with carotid artery intima–media thickness (CIMT), a predictor of atherosclerosis and stroke risk. Gene expression in whole blood was measured using Affymetrix expression arrays in men (n = 17) and women (n = 35), aged 45–64 years, with at least one risk factor for stroke. Mean average CIMT was measured using B-mode ultrasound. Expression levels of 746 genes positively and 292 genes negatively correlated with CIMT only in women (p < 0.05); 881 genes positively and 597 genes negatively correlated with CIMT only in men (p < 0.05). Forty-one genes correlated with CIMT in men and women, but in opposite directions. These genes were associated with estrogen, cholesterol and lipid metabolism, inflammation, coagulation, and vasoreactivity. This pilot study provides the first proof of principle that gene expression in blood cells correlates with CIMT. These results point to potential pathophysiological mechanisms underlying sex differences in stroke risk. Since the sample size is small, the findings are preliminary and need to be confirmed in independent, larger studies.
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Acknowledgments
We thank Ryan Davis and Jeff Gregg of the UC Davis Genomics Core for processing the microarrays. We also thank the many individuals in the Sharp group who helped teach the skills needed to do the analyses.
Sources of Funding
RJT is supported by a National Health and Medical Research Council (Australia; 519365) Postdoctoral fellowship. CDB and the SAVVY study are supported by NIH/NINDS K02 NS058760. FRS is supported by NIH/NINDS-NS056302 and the American Heart Association Bugher Foundation.
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Online Table 1
Genes positively correlated with CIMT in women. (XLS 270 kb)
Online Table 2
Genes positively correlated with CIMT in men. (XLS 380 kb)
Online Table 3
Genes negatively correlated with CIMT in women. (XLS 175 kb)
Online Table 4
Genes negatively correlated with CIMT in men. (XLS 251 kb)
Online Table 5
Genes negatively correlated with CIMT in both men and women. (XLS 21 kb)
Online Table 6
Genes positively correlated with CIMT in both men and women. (XLS 35 kb)
Online Table 7
Canonical pathway analysis of genes posititvely correlated with CIMT in both men and women. (XLS 30 kb)
Online Table 8
Canonical pathway analysis of genes negatviely correlated with CIMT in men and women. (XLS 26 kb)
Online Table 9
Canonical pathway analysis of genes differnentially correlated between men and women. (XLS 35 kb)
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Turner, R.J., Bushnell, C.D., Register, T.C. et al. Gender-Dependent Correlations of Carotid Intima–Media Thickness with Gene Expression in Blood. Transl. Stroke Res. 2, 171–178 (2011). https://doi.org/10.1007/s12975-011-0066-4
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DOI: https://doi.org/10.1007/s12975-011-0066-4