Abstract
ObjectiveIgG Fc receptors (FcγRs) play important roles in immune responses. It is not clear whether FcγR receptors play a role in human asthma and allergy. The aim of current study was to investigate whether functional single nucleotide polymorphisms (SNPs) of FcγR genes (FCGR) are associated with human asthma and allergy.MethodsFunctional SNPs of FCGR2A (FcγRIIA-131His>Arg, rs1801274), FCGR2B (FcγRIIB-187Ile>Thr, rs1050501), FCGR2C (FcγRIIC-13Gln>Stop, rs10917661), FCGR3A (FcγRIIIA-158Val>Phe, rs396991), and FCGR3B variants (FcγRIIIB NA1 and NA2) were genotyped in an asthma family cohort including 370 atopy positive, 239 atopy negative, and 169 asthma positive subjects. The genotype and phenotype data (asthma, bronchial hyper-responsiveness, and atopy) of subjects were analyzed using family-based association tests (FBAT) and logistic regression adjusted for age and sex.ResultThe FcγRIIA-131His>Arg SNP is significantly associated with atopy in a family-based association test (P = 0.00287) and in a logistic regression analysis (P = 0.0269, OR 0.732, 95% CI: 0.555–0.965). The FcγRIIA-131His (or rs1801274-A) allele capable of binding human IgG2 has a protective role against atopy. In addition, the rare FcγRIIB-187Thr (or rs1050501-C) allele defective for the receptor-mediated inhibitory signals is a risk factor for atopy (P = 0.0031, OR 1.758, 95% CI: 1.209–2.556) and IgE production (P<0.001). However, variants of activating FcγRIIIA (rs396991), and FcγRIIIB (NA1 and NA2), and FcγRIIC (rs10917661) are not associated with asthma, BHR, and atopy (P>0.05).ConclusionsFcγRIIA and FcγRIIB functional polymorphisms may have a role in the pathogenesis of allergy.
Highlights
Asthma is a complex syndrome characterized by airflow obstruction, bronchial hyper-responsiveness (BHR), and airway inflammation
FccRIIA and FccRIIB functional polymorphisms may have a role in the pathogenesis of allergy
Conditional logistic regression analysis estimated an OR of 0.732 (P = 0.027, 95% CI: 0.555–0.965) for FCGR2A single nucleotide polymorphisms (SNPs) with atopy, suggesting a protective role against atopy for carriers of the FccRIIA-131His allele
Summary
Asthma is a complex syndrome characterized by airflow obstruction, bronchial hyper-responsiveness (BHR), and airway inflammation. Both genetic and environmental factors contribute to the development of asthma. 48–79% of asthma risk is attributable to genetic factors [1,2]. Allergic reactions to foreign antigens are considered as the most common causes for asthma. No genes have been definitely shown to influence asthma/allergy development. It is well-known that IgE and its cognate receptor (FceRI) are important mediators in allergic reactions [3]. The role of human IgG Fc receptors (FccRs) in asthma and allergy remains unknown
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