Fcγ受体基因多态性与非人类免疫缺陷病毒相关隐球菌病易感性的关联分析

Association between FCGR polymorphisms and the susceptibility to cryptococcosis in human immunodeficiencyvirus-uninfected patients

目的探讨Fcγ受体（FcγR）基因多态性与隐球菌病易感性的关系。方法非HIV相关隐球菌病患者198例作为病例组，门诊体格检查者190名作为健康对照组。隐球菌病患者中颅内感染者117例，颅外感染者81例。提取受试者外周血白细胞DNA，采用多重SNaPshot单核苷酸多态性（SNP）分型技术，对4种FcγR基因多态性FCGRZA13lH／R、FCGR3A158F／V、FCGR3BNAl／NA2和FCGR2B232I／T进行基因分型。比较病例组与健康对照组、颅内感染者与颅外感染者FcTR基因多态性的分布差异。病例组与健康对照组比较采用y。检验或Fisher确切概率检验。结果与健康对照组比较，FCGR2B232I／1基因型在所有隐球菌脑膜炎患者中比例（65％比53％，x2=4．27，p=0．039，OR=1．652，95％CI：1．02～2．67）及免疫功能正常隐球菌脑膜炎患者中比例（69％比53％，X2=4．53，P=0．033，OR=1．958，95％CI：1．05～3．66）均明显增加；FCGR2B232I／T基因型在所有隐球菌脑膜炎患者中比例（27％比40％，X2=5．77，P=0．016，OR=0．542，95％CI：0．33～0．90）及免疫功能正常隐球菌脑膜炎患者中比例（24％比40％，X2=5．14，P=0．023，OR=0．467，95％CI：0．24～O．91）均明显减少。与颅外感染者比较，颅内感染者FCGR2A131R／R基因型比例明显升高（19％比6％，X2=6．48，P=0．011，OR=3．52，95％CI：1．27～9．73）；在免疫功能正常颅内感染者中FCGR2B232I／I基因型比例明显升高（69％比47％，X2=5．47，P=0．019，OR=2．479，95％CI：1．15～5．34）；FCGR2B232I／T基因型在所有颅内感染者中比例（27％比46％，X2=7．56，P=0．006，OR=0．431，95％CI：O．24～0．79）及免疫功能正常颅内感染者中比例（24％比51％，X2=8．66，P=0．003，OR=0．307，95％CI：0．14～O．68）均明显降低。结论隐球菌病患者中的颅内感染与FCGR2A131H／R、FCGR2B232I／T基因多态性存在相关，提示FcγRⅡA、FcγRⅡB这两种受体在隐球菌病的发生发展中可能起重要作用。

Objective To describe immunodeficiency virus （ HIV）-uninfected association of FCGR polymorphisms with the distributions of FCGR polymorphisms in human patients with cryptococcosis, and to investigate the the susceptibility to cryptococcosis. Methods The distributions of the four functional polymorphisms, including FCGR2A 131H/R, FCGR3A 158F/V, FCGR3B NA1/NA2, and FCGR2B 232I/T were compared between 198 cryptococcosis patients and 190 healthy controls. The polymorphisms distribution patterns were also compared between patientswith central nervous system （CNS） infection and those without CNS infection. Genotyping of eight single nucleotide polymorphism （SNP） in FCGR were performed by multiplex SNaPshot technology using DNA extracted from blood samples. The comparison between patients and controls was performed by chi square test or Fisher exact test. Results Compared to healthy controls, the frequency of FCGR2B 232I/I increased （65% vs 53%, ）/2 =4. 27,P=0. 039, OR=I. 652, 95%CI： 1.02-2.67） and that of FCGR2B 232I/T decreased （27% vs 40%, X2=5.77, P=0. 016. OR= 0. 542, 95%CI： O. 33- 0. 90） in patients with cryptococcal meningitis. Among immunocompetent patients, the frequency of FCGR2B 232I/I was also over-presented （69% vs 53%,X2 = 4. 53, P= 0.033, OR=I. 958, 95%CI： 1.05-3. 66） and the FCGR2B 232I/T genotype was also less frequently observed （24% vs 40%,）X2=5.14,P=0. 023, OR=O. 467, 95%CI： O. 24-0.91） compared to healthy controls. There were 117 cases with CNS infection and 81 non-CNS infection cases. The genotype of FCGR2A 131R/R was over-presented （19% vs 6%, ）/2 = 6.48, P = 0. 011, OR = 3.52, 95M CI： 1.27-9.73） and the FCGR2B 232I/T genotype was under-presented （27 % vs 46 %, ）/2 = 7.56, P = 0. 006, OR=O. 431, 95% CI： O. 24- 0. 79） in patients with CNS infection compared with those without CNS infection. Furthermore, the frequency of FCGR2B 232I/I genotypes increased （69% vs 47% ,）/2 =5.47, P=0. 019, OR=2. 479, 95%CI： 1.15-5.34） and the frequency of FCGR2B 232I/T decreased （24% vs 51%,Z2 =8.66,P=0. 003, OR=O. 307, 95%CI： 0. 14-0.68） in immunocompetent patients with CNS infection compared with those without CNS infection. Condusions FCGR2A 131H/R and FCGR2B 232I/T are associated with the susceptibility to cryptococcal CNS infection, which suggests that Fc）＇RRA and Fc）＇RIIB may contribute to the pathogenesis of cryptococcosis.