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

Suzette 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 Citations (Scopus)

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 2007
Externally publishedYes

Fingerprint

National Heart, Lung, and Blood Institute (U.S.)
Chromosomes, Human, Pair 3
Chemokine CCL2
Chemokine Receptors
Multigene Family
Smoking
CCR2 Receptors
Odds Ratio
Chromosomes, Human, Pair 5
LDL Receptors
Genetic Markers
Atherosclerosis
Genome
Ligands
Inflammation
Phenotype
Mutation
hydroquinone

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

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

In: Genes and Immunity, Vol. 8, No. 8, 12.2007, p. 684-690.

Research output: Contribution to journalArticle

Bielinski, SJ, Pankow, JS, Miller, MB, Hopkins, PN, Eckfeldt, JH, Hixson, J, Liu, Y, Register, T, Myers, RH & Arnett, DK 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, vol. 8, no. 8, pp. 684-690. https://doi.org/10.1038/sj.gene.6364434
Bielinski, Suzette 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. / Circulating MCP-1 levels shows linkage to chemokine receptor gene cluster on chromosome 3 : The NHLBI Family Heart Study follow-up examination. In: Genes and Immunity. 2007 ; Vol. 8, No. 8. pp. 684-690.
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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.",
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