Functional Fcgamma Receptor Polymorphisms Are Associated with Human Allergy

Objective
IgG 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.
Methods
Functional 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.
Result
The 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).
Conclusions
FcγRIIA and FcγRIIB functional polymorphisms may have a role in the pathogenesis of allergy.

研究目的
IgG Fc受体（Immunoglobulin G Fc receptors, FcγRs）在免疫应答中发挥重要作用。目前尚不明确FcγR是否参与人类哮喘与过敏性疾病的发生。本研究旨在探究FcγR基因（FCGR）的功能性单核苷酸多态性（single nucleotide polymorphisms, SNPs）与人类哮喘及过敏性疾病的关联。

研究方法
对FCGR2A（FcγRIIA-131His>Arg，rs1801274）、FCGR2B（FcγRIIB-187Ile>Thr，rs1050501）、FCGR2C（FcγRIIC-13Gln>Stop，rs10917661）、FCGR3A（FcγRIIIA-158Val>Phe，rs396991）以及FCGR3B变体（FcγRIIIB NA1与NA2）进行基因分型。本研究的哮喘家系队列纳入特应性阳性受试者370例、特应性阴性受试者239例、哮喘阳性受试者169例。采用基于家系的关联分析（family-based association tests, FBAT）以及校正年龄与性别的logistic回归模型，对受试者的基因型与表型数据（哮喘、支气管高反应性及特应性）进行分析。

研究结果
FcγRIIA-131His>Arg多态性在基于家系的关联分析（P=0.00287）及logistic回归分析（P=0.0269，OR=0.732，95%置信区间（95% confidence interval, 95% CI）：0.555~0.965）中均与特应性呈显著关联。能够结合人IgG2的FcγRIIA-131His（即rs1801274-A）等位基因对特应性具有保护作用。此外，存在受体介导抑制信号缺陷的罕见FcγRIIB-187Thr（即rs1050501-C）等位基因是特应性（P=0.0031，OR=1.758，95%置信区间：1.209~2.556）与IgE生成（P<0.001）的危险因素。然而，活化型FcγRIIIA（rs396991）、FcγRIIIB（NA1与NA2）及FcγRIIC（rs10917661）的变体与哮喘、支气管高反应性及特应性均无显著关联（P>0.05）。

研究结论
FcγRIIA与FcγRIIB的功能性多态性可能参与过敏性疾病的发病机制。