A unifying role of inflammation in chronic diseases including cardiovascular disease, diabetes, hypertension and obesity is emerging. In the VIVA GWAS, variants in six genes were associated with proinflammatory markers. Our findings support a major role of Duffy antigen receptor for chemokines (DARC) in the regulation of the circulating levels of the cysteine-cysteine (CC) chemokine, MCP-1 (effect size = ∼10%). In circulation, MCP-1 is bound to erythrocyte DARC that acts as a chemokine receptor/reservoir of proinflammatory cytokines [48]. Our strongest association for MCP-1 was with a nonsynonymous, highly conservedSNP in DARC (rs12075; MAF = 0.44) which replicated results from the Framingham Heart Study GWAS in Caucasian adults [49]. MCP-1 was also associated with SNPs in GREB1, DFNB31, RASGEF1A, and CCR3. Huber et al. found increased expression of CCR3 in subcutaneous and visceral adipose tissue in obese patients compared to lean controls [50]. Studies by Schnabel et al [49] and Naitza et al. [51] found suggestive associations of serum MCP-1 with CCR2 which is also a MCP-1 receptor and is in the same region of chromosome 3 as CCR3, and referred to as the CCR2/CCR3 cytokine receptor gene cluster.
