Circulating MCP-1 levels shows linkage to chemokine receptor gene cluster on chromosome 3: the NHLBI family heart study follow-up examination.
Atherogenesis is a chronic inflammatory process. Critical in the inflammation process is monocyte chemoattractant protein-1 (MCP-1). To locate genomic regions that affect circulating MCP-1 levels, a genome-wide linkage scan was conducted in a sample of whites and blacks. Phenotype and genetic marker data were available for 2501 white and 513 black participants in the National Heart Lung Blood Institute Family Heart Study follow-up examination. Heritability for MCP-1 was 0.37 in whites and 0.47 in blacks after adjusting for the effects of sex, age, age-sex interaction, smoking status, lifetime smoking exposure (pack-years) and field center. Significant linkage was observed for MCP-1 in a combined black and white sample on chromosome 3 (logarithm of the odds ratio (LOD)=3.5 at 78 cM, P=0.0001) and suggestive linkage was observed in whites on chromosome 5 (LOD=1.8 at 128 cM, P=0.002). Located under the linkage peak on chromosome 3 is the chemokine receptor gene cluster, including CCR2, the receptor for MCP-1. This study provides preliminary evidence linking genetic variation in a receptor to circulating levels of its ligand, as previously demonstrated for the low-density lipoprotein receptor. Further characterization of these chromosomal regions is needed to identify the functional mutations associated with circulating levels of MCP-1.
Bielinski
S J
SJ
Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55454, USA. bielinski@epi.umm.edu
Pankow
J S
JS
Miller
M B
MB
Hopkins
P N
PN
Eckfeldt
J H
JH
Hixson
J
J
Liu
Y
Y
Register
T
T
Myers
R H
RH
Arnett
D K
DK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000235:genetics*; D044383:Black People / Q000235:genetics; D018932:Chemokine CCL2 / Q000097:blood*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D054555:National Heart, Lung, and Blood Institute (U.S.); D019707:Receptors, Chemokine / Q000235:genetics*; D014481:United States / Q000208:ethnology; D044465:White People / Q000235:genetics; D001741:Black or African American
D018932:Chemokine CCL2; D019707:Receptors, Chemokine