Circulating MCP-1 levels shows linkage to chemokine receptor gene cluster on chromosome 3: The NHLBI Family Heart Study follow-up examination

S. J. Bielinski, J. S. Pankow, M. B. Miller, P. N. Hopkins, J. H. Eckfeldt, J. Hixson, Y. Liu, T. Register, R. H. Myers, D. K. Arnett

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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 78cM, P=0.0001) and suggestive linkage was observed in whites on chromosome 5 (LOD=1.8 at 128cM, 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.

Original languageEnglish (US)
Pages (from-to)684-690
Number of pages7
JournalGenes and Immunity
Volume8
Issue number8
DOIs
StatePublished - Dec 1 2007

ASJC Scopus subject areas

  • Immunology
  • Genetics
  • Genetics(clinical)

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    Bielinski, S. J., Pankow, J. S., Miller, M. B., Hopkins, P. N., Eckfeldt, J. H., Hixson, J., Liu, Y., Register, T., Myers, R. H., & Arnett, D. K. (2007). Circulating MCP-1 levels shows linkage to chemokine receptor gene cluster on chromosome 3: The NHLBI Family Heart Study follow-up examination. Genes and Immunity, 8(8), 684-690. https://doi.org/10.1038/sj.gene.6364434