Gene expression variation between African Americans and whites is associated with coronary artery calcification: the multiethnic study of atherosclerosis

Abstract

Coronary artery calcium (CAC) is a strong indicator of total atherosclerosis burden. Epidemiological data have shown substantial differences in CAC prevalence and severity between African Americans and whites. However, little is known about the molecular mechanisms underlying initiation and progression of CAC. Microarray gene expression profiling of peripheral blood leucocytes was performed from 119 healthy women aged 50 yr or above in the Multi-Ethnic Study of Atherosclerosis cohort; 48 women had CAC score >100 and carotid intima-media thickness (IMT) >1 mm, while 71 had CAC <10 and IMT <0.65 mm. When 17 African Americans were compared with 41 whites in the low-CAC group, 409 differentially expressed genes (false discovery rate <5%) were identified. In addition, 316 differentially expressed genes were identified between the high- and low-CAC groups. A substantial overlap between these two gene lists was observed (148 genes, P < 10(-6)). Furthermore, genes expressed lower in African Americans also tend to express lower in individuals with low CAC (correlation 0.69, P = 0.002). Ontology analysis of the 409 race-associated genes revealed significant enrichment in mobilization of calcium and immune/inflammatory response (P < 10(-9)). Of note, 25 of 30 calcium mobilization genes were involved in immune/inflammatory response (P < 10(-10)). Our data suggest a connection between immune response and vascular calcification and the result provides a potential mechanistic explanation for the lower prevalence and severity of CAC in African Americans compared with whites.

Molecular Mechanisms of Arterial Stiffening

“…Alternatively, there may be a direct correlation between gene expression in circulating leukocytes that participate in the pathogenesis of arteriosclerosis. In agreement with this, previous microarray data from Huang et al [48] have identified the differential expression of several genes in circulating cells, including calcium- and bone-related genes, in individuals with and without vascular calcification.…”

Has Our Understanding of Calcification in Human Coronary Atherosclerosis Progressed?

“…45 There may be inherent genetic predisposition for coronary calcification in blacks and whites, which remains to be determined. Huang et al 46 showed that race-related genes, such as GAB2, which is expressed at a lower level in blacks and also in those with low calcification may be another explanation for the lower prevalence of calcification in blacks. Furthermore, it has been reported that soluble epoxide hydroxylase gene polymorphism is associated with coronary calcification in blacks, but not in whites.…”

Family history of coronary heart disease and the incidence and progression of coronary artery calcification: Multi-Ethnic Study of Atherosclerosis (MESA)

“…Additional studies are needed to better understand how the respective potential genetic loci and environmental factors entailed in family history and race/ethnicity interact with one another and how these affect clinically relevant endpoints. In this regard, one study has examined whole-blood gene expression profiles and CAC levels among white and African American women selected from MESA participants [49]. The study found concordantly decreased expression profiles of several genes in African Americans, particularly those involved in immunologic and inflammatory pathways, when compared to the overall multi-racial low CAC score group.…”