Association Study Of GARP(LRRC32) Polymorphisms With Dust Mite-sensitized Persistent Allergic Rhinitis In A Chinese Han Population

BACKGROUND: Allergic rhinitis is a common inflammatory disease of the upper airway, in which both genetic and environmental factors contribute to the pathogenesis. Recent GWASs have convincingly detected a novel locus associated with allergic diseases. GARP(LRRC32) in this susceptibility locus suggests a role for autoimmune and allergic diseases through biological ways involved in the immunosuppression effect of regulatory T cells.OBJECTIVES: To evaluate the association of GARP polymorphisms with persistent allergic rhinitis(PER) due to house dust mite in a Chinese Han population.METHODS: In a hospital-based case-control study of 534 patients with mitesensitized PER and 451 healthy controls from Jiangsu and Anhui provinces, we genotyped six single nucleotide polymorphisms(SNPs) in GARP. We also measured serum levels of eosinophil cationic protein, total Ig E and allergic-specific IgE against Dermatophagoides pteronyssinus and Dermatophagoides farinae using ImmunoCAP assays.RESULTS: In the single locus study, rs79525962 was significantly associated with mite-sensitized PER(P<0.05). Moreover, rs79525962 was associated with significantly increased risk of nonasthmatic PER(adjusted OR=1.454, 95%CI=1.052-2.010). We also found the individuals with CC genotype of rs3781699 had a significant lower risk of mite-sensitized PER compared to those with AA genotype(adjusted OR=0.646, 95%CI= 0.427-0.976), but no statistical evidence was observed for the association of rs3781699 with mite-sensitized PER(P>0.05). Further stratification analysis showed rs79525962 was associated with significantly increased risk of mite-sensitized PER in the subgroup of age <18 years(adjusted OR=1.706, 95%CI=1.090-2.671), and this increased risk was also found in the females(adjusted OR=1.729, 95%CI=1.042-2.869).CONCLUSIONS: SNP rs79525962 in GARP appears to mark a genuine mitesensitized PER risk locus and the GARP gene may contribute to susceptibility of mitesensitized PER in this Chinese Han population. Further functional analyses are required to determine the underlying genetic molecule mechanisms, which may provide new insights into the pathogenesis of mite-sensitized PER.