Circulating soluble ICAM-1 levels shows linkage to ICAM gene cluster region on chromosome 19: the NHLBI Family Heart Study follow-up examination.
Atherogenesis is a chronic inflammatory process in which intercellular adhesion molecule 1 (ICAM-1) plays a critical role. Circulating soluble ICAM-1 (sICAM-1) is thought to be the result of cleavage of membrane-bound ICAM-1 and its concentration in serum/plasma has been shown to be heritable. Genome-wide linkage scans were conducted for quantitative trait loci influencing sICAM-1. Phenotype and genetic marker data were available for 2617 white and 531 black individuals in the NHLBI Family Heart Study follow-up examination. Heritability for sICAM-1 was 0.39 in whites and 0.59 in blacks. Significant linkage was observed on chromosome 19 (LOD=4.0 at 14cM) in whites near the ICAM gene cluster that includes the structural gene for ICAM-1. The T-allele of ICAM-1 SNP rs5491 has been strongly associated with the specific sICAM-1 assay we used in our study. Through additional genotyping we were able to rule out rs5491 as the cause of the linkage finding. This study provides preliminary evidence linking genetic variation in the ICAM1 structural gene to circulating sICAM-1 levels.
Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA. Bielinski@epi.umn.edu
Suzette J
SJ
Bielinski
James S
JS
Pankow
Catherine Leiendecker
CL
Foster
Michael B
MB
Miller
Paul N
PN
Hopkins
John H
JH
Eckfeldt
Jim
J
Hixson
Yongmei
Y
Liu
Tom
T
Register
Richard H
RH
Myers
Donna K
DK
Arnett
D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism; D044383:Black People / Q000235:genetics; D002888:Chromosomes, Human, Pair 19; D005260:Female; D005500:Follow-Up Studies; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D010641:Phenotype; D012995:Solubility; D014657:Vasculitis / Q000235:genetics* / Q000378:metabolism; D044465:White People / Q000235:genetics
D018799:Intercellular Adhesion Molecule-1