Circulating soluble ICAM-1 levels shows linkage to ICAM gene cluster region on chromosome 19: The NHLBI Family Heart Study follow-up examination

Suzette J. Bielinski, James S. Pankow, Catherine Leiendecker Foster, Michael B. Miller, Paul N. Hopkins, John H. Eckfeldt, Jim Hixson, Yongmei Liu, Tom Register, Richard H. Myers, Donna K. Arnett

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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 14 cM) 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.

Original languageEnglish (US)
Pages (from-to)172-178
Number of pages7
JournalAtherosclerosis
Volume199
Issue number1
DOIs
StatePublished - Jul 2008

Bibliographical note

Funding Information:
We are grateful for resources from the University of Minnesota Supercomputing Institute, the NIH Training Grant in Cardiovascular Disease Genetic Epidemiology (#5 T32 HL007972). Support was provided by the National Heart, Lung, and Blood Institute cooperative agreement grants U01 HL67893, U01 HL67894, U01 HL67895, U01 HL67896, U01 HL67897, U01 HL67898, U01 HL67899, U01 HL67900, U01 HL67901, U01 HL67902. Support was also partially provided by the National Heart, Lung, and Blood Institute cooperative agreement grants U01 HL56563, U01 HL56564, U01 HL56565, U01 HL56566, U01 HL56567, U01 HL56568, U01 HL56569. This report is presented on behalf of the investigators of the NHLBI Family Heart Study. The investigators thank the study participants and staff for their valuable contributions.

Keywords

  • Atherosclerosis
  • ICAM gene cluster
  • Inflammation
  • Intercellular adhesion molecule-1
  • Linkage (genetics)

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