Duffy antigen receptor for chemokines (Darc) polymorphism regulates circulating concentrations of monocyte chemoattractant protein-1 and other inflammatory mediators

Abstract

To identify the genetic basis of circulating concentrations of monocyte chemoattractant protein-1 (MCP-1), we conducted genome-wide association analyses for MCP-1 in 3 independent cohorts (n ‫؍‬ 9598). The strongest association was for serum MCP-1 with a nonsynonymous polymorphism, rs12075 (Asp42Gly) in DARC, the gene for Duffy antigen receptor for chemokines, a known vascular reservoir of proinflammatory cytokines (minor allele frequency, 45.6%; P < 1.0 * 10 ؊323 ). This association was supported by family-based genetic linkage at a locus encompassing the DARC gene (genome-wide P ‫؍‬ 8.0 * 10 ؊13 ).

COX-2 promotes metastasis in nasopharyngeal carcinoma by mediating interactions between cancer cells and myeloid-derived suppressor cells

“…38 After TW03 or CNE2 cells were co-cultured with T-MDSCs for 48 h, the expression of EMT-like cellular markers was altered in TW03 and CNE2 cells, including a dramatic upregulation of COX-2, the mesenchymal markers vimentin and fibronectin and the EMT-associated transcription factor snail along with the downregulation of the epithelial marker E-cadherin, as shown in Fig. 4F.…”

Strontium Ranelate in the Treatment of Postmenopausal Osteoporosis: Impact of Vitamin D Receptor and Monocyte Chemoattractant Protein-1 Gene Polymorphisms on Bone Mineral Density: A Pilot Study

“…При изучении генетической природы уровня белка МСР-1 в крови R. Schnable [19] показал на трех незави-симых когортах его сильную ассоциацию с полимор-физмом Arg42Gly гена Darc. Этот ген кодирует эритро-цитарный рецептор антигена Duffy для хемокинов, из-вестный как резервуар провоспалительных цитокинов.…”

The DARC side of GWAS

“…6 They began with a large genome-wide association study of unrelated subjects, one that has combined set of scans, that some refer to as "supersized" GWAS. Follow-up in a family-based analysis (generally preferred by classical geneticists) confirmed the association, giving it even more traction.…”

“…These cells collectively define "hematopoietic niches" and include cells of the osteoblastic lineage, vascular endothelium, and cells of the sympathetic nervous system. [3][4][5][6][7] The relative importance of each of these components has been a point of debate, and new concepts are emerging on their specific roles supporting hematopoiesis at different levels and in different physiologic conditions. To identify which of these compartment(s) could be affected by the GVHD process, the authors made a comparative histologic analysis of the bone marrow in animals with GVHD and control counterparts.…”