Genome scan of systemic biomarkers of vascular inflammation in the Framingham Heart Study: evidence for susceptibility loci on 1q.
Vascular inflammation plays a central role in atherosclerosis and inflammatory biomarkers predict risk of cardiovascular disease (CVD). Thus, finding genes that influence systemic levels of inflammatory biomarkers may provide insights into genetic determinants of vascular inflammation and CVD. We conducted variance-component linkage analyses of blood levels of four biomarkers of vascular inflammation [C-reactive protein (CRP), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1)] in 304 extended families from the Framingham Heart Study, using data from a 10cM genome scan. We computed p-values by a permutation approach. Heritability estimates ranged from 14% (IL-6) to 44% (MCP-1) after log transforming and adjusting for covariates. Significant linkage to MCP-1 was found on chromosome 1 (LOD=4.27 at 186cM; genome-wide p=0.005), in a region containing inflammatory candidate genes such as SELE, SELP (E- and P-selectin) and CRP. Other linkage peaks with LOD scores >2 were found for MCP-1 on chromosome 1 (LOD=2.04 at 16cM; LOD=2.34 at 70cM) and chromosome 17 (LOD=2.44 at 22cM) and for sICAM-1 on chromosome 1 at 229cM (LOD=2.09) less than 5cM from the interleukin-10 (IL10) gene. Multiple genes on chromosome 1 may influence inflammatory biomarker levels and may have a potential role in development of CVD.
Dupuis
Josée
J
Department of Biostatistics, Boston University School of Public Health, 715 Albany Street, Boston, MA 02118, USA. dupuis@bu.edu
Larson
Martin G
MG
Vasan
Ramachandran S
RS
Massaro
Joseph M
JM
Wilson
Peter W F
PW
Lipinska
Izabella
I
Corey
Diane
D
Vita
Joseph A
JA
Keaney
John F
JF
Benjamin
Emelia J
EJ
D000368:Aged; D002878:Chromosomes, Human, Pair 1; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D023281:Genomics; D006801:Humans; D008126:Lod Score; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D012307:Risk Factors; D014657:Vasculitis / Q000453:epidemiology* / Q000235:genetics*
D005819:Genetic Markers