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

V. Saroja Voruganti, Sandra Laston, Karin Haack, Nitesh R. Mehta, C. Wayne Smith, Shelley A. Cole, Nancy F. Butte, Anthony G. Comuzzie

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    Abstract

    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 4-19years, 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.

    Original languageEnglish (US)
    Pages (from-to)634-638
    Number of pages5
    JournalCytokine
    Volume60
    Issue number3
    DOIs
    StatePublished - Dec 1 2012

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    Keywords

    • Effect size
    • Inflammation
    • Obesity
    • Polymorphism
    • Variance

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology
    • Biochemistry
    • Hematology
    • Molecular Biology

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