Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
PLoS One. 2012;7(8):e42439. doi: 10.1371/journal.pone.0042439. Epub 2012 Aug 3.
As important regulators of the immune system, the human Fcγ receptors (FcγRs) have been demonstrated to play important roles in the pathogenesis of various infectious diseases. The aim of the present study was to identify the association between FCGR polymorphisms and cryptococcal meningitis.
METHODOLOGY/PRINCIPAL FINDINGS: In this case control genetic association study, we genotyped four functional polymorphisms in low-affinity FcγRs, including FCGR2A 131H/R, FCGR3A 158F/V, FCGR3B NA1/NA2, and FCGR2B 232I/T, in 117 patients with cryptococcal meningitis and 190 healthy controls by multiplex SNaPshot technology. Among the 117 patients with cryptococcal meningitis, 59 had predisposing factors. In patients with cryptococcal meningitis, the FCGR2B 232I/I genotype was over-presented (OR = 1.652, 95% CI [1.02-2.67]; P = 0.039) and the FCGR2B 232I/T genotype was under-presented (OR = 0.542, 95% CI [0.33-0.90]; P = 0.016) in comparison with control group. In cryptococcal meningitis patients without predisposing factors, FCGR2B 232I/I genotype was also more frequently detected (OR = 1.958, 95% CI [1.05-3.66]; P = 0.033), and the FCGR2B 232I/T genotype was also less frequently detected (OR = 0.467, 95% CI [0.24-0.91]; P = 0.023) than in controls. No significant difference was found among FCGR2A 131H/R, FCGR3A 158F/V, and FCGR3B NA1/NA2 genotype frequencies between patients and controls.
CONCLUSION/SIGNIFICANCE: We found for the first time associations between cryptococcal meningitis and FCGR2B 232I/T genotypes, which suggested that FcγRIIB might play an important role in the central nervous system infection by Cryptococcus in HIV-uninfected individuals.
作为免疫系统的重要调节因子,人类 Fcγ 受体(FcγRs)已被证明在各种传染病的发病机制中发挥重要作用。本研究旨在确定 FCGR 多态性与隐球菌性脑膜炎之间的关联。
方法/主要发现:在这项病例对照遗传关联研究中,我们通过多重 SNaPshot 技术,对 117 例隐球菌性脑膜炎患者和 190 例健康对照者的低亲和力 FcγR 中的 4 个功能多态性(FCGR2A 131H/R、FCGR3A 158F/V、FCGR3B NA1/NA2 和 FCGR2B 232I/T)进行了基因分型。在 117 例隐球菌性脑膜炎患者中,有 59 例有易感因素。与对照组相比,在隐球菌性脑膜炎患者中,FCGR2B 232I/I 基因型过度表达(OR=1.652,95%CI[1.02-2.67];P=0.039),FCGR2B 232I/T 基因型表达不足(OR=0.542,95%CI[0.33-0.90];P=0.016)。在无易感因素的隐球菌性脑膜炎患者中,FCGR2B 232I/I 基因型也更频繁地检测到(OR=1.958,95%CI[1.05-3.66];P=0.033),而 FCGR2B 232I/T 基因型也较少检测到(OR=0.467,95%CI[0.24-0.91];P=0.023)。在患者和对照组之间,FCGR2A 131H/R、FCGR3A 158F/V 和 FCGR3B NA1/NA2 基因型频率没有显著差异。
结论/意义:我们首次发现隐球菌性脑膜炎与 FCGR2B 232I/T 基因型之间存在关联,这表明 FcγRIIB 可能在 HIV 阴性个体的隐球菌性中枢神经系统感染中发挥重要作用。