Association of Single-Nucleotide Polymorphisms in DC-SIGN with Nasopharyngeal Carcinoma Susceptibility

Abstract

The aim of this study was to explore potential relationships of four single-nucleotide polymorphisms (SNPs) in the gene encoding dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) with risk of nasopharyngeal carcinoma (NPC). The DC-SIGN SNPs rs7252229, rs4804803, rs2287886, and rs735240 were genotyped in 477 unrelated NPC patients and 561 cancer-free controls. At rs7252229, risk of NPC was significantly lower in individuals with GC (odds ratio [OR] 0.076, 95% confidence interval [CI] 0.008–0.690), GG (OR 0.056, 95%CI 0.006–0.487), or GC + GG (OR 0.059, 95%CI 0.007–0.515) than in individuals with the CC genotype, after adjusting for age, gender, smoking history, and EBV-VCA-IgA status. At rs4804803, risk of NPC was significantly higher in individuals with the genotype GG than in those with the genotype AA (adjusted OR 9.038, 95%CI 1.708–47.822). At rs735240, risk of NPC did not change significantly with genotypes AG, GG, or AG + GG after adjusting for age, gender, and smoking history. However, when data were also adjusted for EBV-VCA-IgA status, three genotypes emerged as associated with significantly higher risk of NPC than the AA genotype: AG (OR 2.976, 95%CI 1.123–7.888), GG (OR 3.314, 95%CI 1.274–8.622), or GG + AG (OR 3.191, 95%CI 1.237–8.230). Our results suggest that DC-SIGN SNPs rs7252229, rs4804803, and rs735240 may influence NPC risk in the Chinese population. The mechanisms mediating this risk require a further study.

Correlation of variable repeat number in the neck regions of DC-SIGN and DC-SIGNR with susceptibility to nasopharyngeal carcinoma in a Chinese population

“… 2 , 13 Polymorphism in parts of DC-SIGN outside the neck region has been linked to NPC risk in a North African population and in Chinese populations from Guangdong and Guangxi. 2 , 3 , 14 Whether the same is true of polymorphism in the neck region is unknown. Here, we provide the first evidence that it may not be associated with NPC risk, at least in a Chinese population.…”

“…Given the high expression of DC-SIGNR on sinusoidal endothelial cells in the lymph node, where B-cell activation occurs, we propose that DC-SIGNR binds to glycans on the EBV surface and thereby traps EBV in the lymph nodes, where the virus interacts with cluster of differentiation 21 on the B-cell surface. 2 , 4 , 8 , 17 – 19 The 9-repeat polymorphism may lead to tighter binding of EBV and therefore more efficient infection of B lymphocytes. The CRD binds multivalent ligands on pathogens with up to 7-fold greater affinity and selectivity when it is tetrameric than when it is monomeric.…”

“… 1 Work from our group and others has suggested an association between NPC risk and single nucleotide polymorphism in the CD209 gene (Gene ID: 30835) encoding dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN). 2 , 3 DC-SIGN is a C-type lectin expressed mainly on monocytes, immature dendritic cells (DCs), certain macrophages, and placental Hofbauer cells. The molecule, which contains intracellular, transmembrane, and extracellular domains, mediates host infection by various pathogens via a carbohydrate recognition domain (CRD) in the extracellular domain.…”

“… 7 It is also possible that variation in the number of neck region repeats affects affinity for binding Epstein–Barr virus (EBV), which contains high-mannose glycoproteins like HIV and is strongly associated with NPC pathogenesis. 2 , 8 – 10 Further work is needed to elucidate how polymorphism of DC-SIGN neck region repeats may contribute to NPC risk.…”

Current Status and Future Perspectives about Molecular Biomarkers of Nasopharyngeal Carcinoma

“…The environmental factors such as dietary pattern and geographic areas may explain the contrasting role of this SNP in NPC susceptibility. Moreover, through genetic analysis, the dendritic cells specific intercellular adhesion molecule 3-grabbing nonintegrin ( DC-SIGN ) gene variants with SNPs rs7252229, rs735240, and rs4804803 were also found to be associated with NPC susceptibility [ 24 , 25 ]. Polymorphism in DC-SIGN with genotype GG at rs735240 and AA at rs2287886 enable dendritic cells to be easily infected by cytomegaloviruses, which have similar a structure to EBV.…”