Some Polymorphisms in Epstein-Barr Virus–induced Gene 3 Modify the Risk for Chronic Rhinosinusitis

Abstract

Forkhead box protein 3 (FOXP3), a transcription factor required for development and function of regulatory T cell, and Epstein-Barr virus-induced gene 3 (EBI3), a downstream target of FOXP3, may be important in the development of chronic rhinosinusitis (CRS) with or without sinonasal polyposis (CRSwNP and CRSsNP, respectively). Our objective was therefore to examine the presence of any associations between specific single nucleotide polymorphisms (SNPs) in/around the FOXP3 and EBI3 genes and risk for CRS in Chinese subjects. A population-based case-control association analysis was performed. DNA extracted from peripheral blood leukocytes from 667 subjects with CRS (360 CRSwNP and 306 CRSsNP) and 330 healthy controls was assessed for SNPs selected and complemented with tagging SNPs. A total of seven SNPs (4 in FOXP3 and 3 in EBI3 genes) were genotyped and genetic association tests were performed. In the single-locus analyses of CRS risk, the allele frequencies of rs428253 (p = 0.0191) in EBI3 gene and rs2232365 (p = 0.0307) and rs3761548 (p = 0.0221) in FOXP3 gene were significantly different between the CRS cases and the controls. Furthermore, genotype association analysis showed a significant protective effect only between EBI3_rs428253 (CG/CC; p = 0.029) and CRS after adjustment. Similarly, stratified analysis of CRS risk on category showed rs428253 of the EBI3 gene to play a protective role among both CRSwNP (CG/CC; p = 0.002) and CRSsNP (GG/CC; p = 0.023) subjects. Haplotype analysis of the FOXP3 gene region further indicated that CRS risk was higher in individuals carrying the haplotype GG in rs2294018-rs2232365 block, compared with wild-type AG haplotype, and AG in rs3761548-4824747 block, compared with wild-type CG haplotype. The findings of this study suggest that SNPs in FOXP3 and EBI3 genes modify the risk for development of CRS.