Gender-Dependent Correlations of Carotid Intima-Media Thickness with Gene Expression in Blood

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.