Association of VDR and CYP2R1 Polymorphisms with Mite-Sensitized Persistent Allergic Rhinitis in a Chinese Population.

Hui-Qin Tian,Chong Shen,Lei Cheng,Mei-Ping Lu,Wen-Min Lu,Han Zhou,Hai-Long Zhao,Xin-Yuan Chen,Ying Lu,Mei-Lin Wang,Zheng-Dong Zhang,Ruo-Xi Chen,Qing-Yi Wei

doi:10.1371/journal.pone.0133162

Abstract

As recent studies have described an association between vitamin D and allergic rhinitis, we hypothesized that vitamin D pathway-related genes may be candidate genes for susceptibility to allergic rhinitis. Thus, we sought to evaluate whether polymorphisms in the vitamin D receptor (VDR) and CYP2R1 genes are associated with mite-sensitized persistent allergic rhinitis (PER) in a Han Chinese population. A hospital-based case-control study consisting of 519 patients with mite-sensitized PER and 447 healthy controls was conducted. Five single nucleotide polymorphisms (SNPs) in VDR and CYP2R1 were selected for genotyping. The genotype and allele frequencies of rs9729, rs2228570, rs1544410, and rs731236 in VDR as well as rs2060793 in CYP2R1 were not significantly associated with susceptibility to mite-sensitized PER. After stratification analyses, however, both the CT and CT/TT genotypes of rs2228570 in VDR exhibited a significantly decreased risk (CT: adjusted odds ratio (OR)=0.58, 95% confidence intervals (CI)=0.37-0.91; CT/TT: adjusted OR=0.61, 95% CI=0.40-0.93) of mite-sensitized PER, while the AA genotype of rs2060793 in CYP2R1 exhibited a significantly increased risk (adjusted OR=1.85, 95% CI=1.03-3.34) of PER in the age subgroup of <16 years old. Both the AG and AG/GG genotypes of rs731236 in VDR exhibited a significantly decreased risk (AG: adjusted OR=0.43, 95% CI=0.21-0.89; AG/GG: adjusted OR=0.46, 95% CI=0.23-0.94) of PER in the female subgroup. Analysis of the locus-locus interactions of VDR and CYP2R1 revealed two models that involved combined SNPs of VDR and CYP2R1 were statistically significant (P<0.05). Our data suggest that age and gender may have an impact on the association of three SNPs (rs2228570, rs731236, and rs2060793) in genes of the vitamin D pathway with the risk of mite-sensitized PER in this Chinese population. The VDR and CYP2R1 variants may be involved in genetic interactions in the pathogenesis of PER.

Highlights

Allergic rhinitis is a symptomatic disorder of the nose and is induced after allergen exposure by an immunoglobulin E (IgE)-mediated inflammation of the membranes lining the nose
Various molecules participate in the phases of an allergic reaction, and as such, many genes encoding those molecules can be candidate genes for allergic rhinitis
Previous reports revealed that several genetic variants of candidate genes, such as ADAM33 [16,17], IL4 [18,19], MRPL4, and TNFA [20], are positively associated with susceptibility to allergic rhinitis

Summary

Introduction

Allergic rhinitis is a symptomatic disorder of the nose and is induced after allergen exposure by an immunoglobulin E (IgE)-mediated inflammation of the membranes lining the nose. Clinical practice guidelines for allergic rhinitis have been developed over the past two decades and have resulted in improved care of patients [3], its exact pathogenesis remains unclear. Both environmental factors and genetic susceptibility are thought to play critical roles in the development of allergic rhinitis. Vitamin D affects the Th1/Th2 balance by inhibiting Th1 cells and augmenting Th2 cell development [9]. Based on these functions, vitamin D may play an important role in the pathogenesis of allergic rhinitis

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