Genome-wide association replicates the association of Duffy antigen receptor for chemokines (DARC) polymorphisms with serum monocyte chemoattractant protein-1 (MCP-1) levels in Hispanic children

Cytokine. 2012 Dec;60(3):634-8. doi: 10.1016/j.cyto.2012.08.029. Epub 2012 Sep 25.


Obesity is associated with a chronic low inflammatory state characterized by elevated levels of chemokines. Monocyte chemoattractant protein-1 (MCP-1) is a member of the cysteine-cysteine (CC) chemokine family and is increased in obesity. The purpose of this study was to identify loci regulating serum MCP-1 in obese Hispanic children from the Viva La Familia Study. A genome-wide association (GWA) analysis was performed in 815 children, ages 4-19 years, using genotypes assayed with the Illumina HumanOmni1-Quad v1.0 BeadChips. All analyses were performed in SOLAR using a linear regression-based test under an additive model of allelic effect, while accounting for the relatedness of family members via a kinship variance component. The strongest association for MCP-1 levels was found with a non-synonymous single nucleotide polymorphism (SNP), rs12075, resulting in an amino acid substitution (Asp42Gly) in the Duffy antigen receptor for chemokines (DARC) gene product (minor allele frequency=43.6%, p=1.3 × 10(-21)) on chromosome 1. Four other DARC SNPs were also significantly associated with MCP-1 levels (p<10(-16)-10(-6)). The Asp42Gly variant was associated with higher levels of MCP-1 and accounted for approximately 10% of its variability. In addition, MCP-1 levels were significantly associated with SNPs in chemokine receptor 3 (CCR3) and caspase recruitment domain family, member 9 (CARD9). In summary, the association of the DARC Asp42Gly variant with MCP-1 levels replicates previous GWA results substantiating a potential role for DARC in the regulation of pro-inflammatory cytokines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Amino Acid Substitution
  • CARD Signaling Adaptor Proteins / genetics
  • Chemokine CCL2 / blood*
  • Chemokine CCL2 / genetics
  • Child
  • Child, Preschool
  • Duffy Blood-Group System / genetics*
  • Female
  • Genome-Wide Association Study
  • Genotype
  • Hispanic or Latino / genetics*
  • Humans
  • Male
  • Obesity / blood
  • Obesity / genetics*
  • Polymorphism, Single Nucleotide
  • Receptors, CCR3 / genetics
  • Receptors, Cell Surface / genetics*
  • Young Adult


  • ACKR1 protein, human
  • CARD Signaling Adaptor Proteins
  • CARD9 protein, human
  • CCL2 protein, human
  • CCR3 protein, human
  • Chemokine CCL2
  • Duffy Blood-Group System
  • Receptors, CCR3
  • Receptors, Cell Surface