title: 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.
authors.affiliation: Department of Preventive Medicine, Northwestern University, Chicago, Illinois, USA. huangcc@northwestern.edu
authors.forename: Chiang-Ching
authors.initials: CC
authors.lastname: Huang
authors.forename: Donald M
authors.initials: DM
authors.lastname: Lloyd-Jones
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Guo
authors.forename: Nalini M
authors.initials: NM
authors.lastname: Rajamannan
authors.forename: Simon
authors.initials: S
authors.lastname: Lin
authors.forename: Pan
authors.initials: P
authors.lastname: Du
authors.forename: Qiquan
authors.initials: Q
authors.lastname: Huang
authors.forename: Lifang
authors.initials: L
authors.lastname: Hou
authors.forename: Kiang
authors.initials: K
authors.lastname: Liu
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000208:ethnology* / Q000235:genetics*; D002114:Calcinosis / Q000150:complications / Q000208:ethnology / Q000235:genetics*; D009202:Cardiomyopathies / Q000150:complications / Q000208:ethnology / Q000235:genetics; D003331:Coronary Vessels / Q000473:pathology*; D003920:Diabetes Mellitus / Q000208:ethnology / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044465:White People / Q000235:genetics*