系统性红斑狼疮候选基因OAZ中单核苷酸多态性的系统筛选及相关分析

目的研究OLFl／EBF相关锌指蛋白基因（OAZ）上的单核苷酸多态性（SNP）与中国人群系统性红斑狼疮（SLE）发病的相关性。方法利用243个中国SLE患者核心家系DNA．依据http：／／www．hapmap．org/数据库中的信息，选取了OAZ基因上的35个SNP位点进行等位基因分型，以Haploview、Genehunter和Fbat生物信息学软件分析其与中国人SLE发病的相关性。结果对等位基因分型结果进行家系传递不平衡检验（TDT），提示rsl420683，rs6500240显示传递不平衡，rsl420683等位基因G优势传递给患者，传递：不传递=86：50，P=0．002；rs6500240等位基因C优势传递给患者，传递：不传递=88：56，P=0．008。结论OAZ基因上的SNP位点rs1420683和rs6500240与SLE发病相关．未发现这两个位点的突变影响转录因子的结合，并且相互之间并没有存在强的连锁关系，可能与邻近的某个影响蛋白结构或表达的功能性SNP存在连锁不平衡，需要进一步研究证实。     

血管紧张素转化酶基因多态性与系统性红斑狼疮相关性研究

目的探讨位于人类17号染色体长臂2区3带(17q23)上的血管紧张素转化酶(ACE)基因多态性G261T与系统性红斑狼疮(SLE)的关系。方法采用聚合酶链反应(PCR)和限制性片段长度多态性(RFLP)方法检测人类17q23上的ACE基因多态性G261T,运用家系为基础的相关性检验(FBAT)方法,对119个中国汉族SLE患者家系(其中核心家系95个,119例患者,316名家系其他成员)ACE多态性位点(rs4303)进行等位基因和基因型分析。结果在119例SLE患者中：G、T等位基凶频率分别是44．8%和55．2%：基因型GG、GT和TT的频率分别是13．9%,62．0%,24．1%。FBAT单位点分析显示G261T多态性与SLE显著相关：附加模型(Z=2．877．P=0．004),显性模型(Z=2．557,P=0．011)以及隐性模型(Z= 2．202,P=0．028)。传递不平衡检验(TDT)和同胞传递不平衡检验(STDT)显示其中ACE-261T等位基因由杂合子父母优势传递给患病子女或者与正常同胞相比更容易传递给患者(X~2=11．66,P=0．001)。结论ACE基因是中国汉族人群SLE的易感基因；其中ACE-261T等位基因与SLE发病相关。     

PBX1基因3''末端基因多态性rs3185695与系统性红斑狼疮发病相关研究

目的研究前B淋巴细胞白血病转录因子(PBX1)3’端单核苷酸多态性(SNP)与中国人系统性红斑狼疮(SLE)发病的相关性。方法对PBX1基因3’端下游区域通过测序发现SNP rs3185695, 再对发现的该SNP进行等位基因分型。以Haploview软件和延伸型传递不平衡试验(ETDT)分析SNP与中国人SLE发病的相关性。结果靠近PBX1 3’末端通过测序发现的SNP rs3185695进行家系传递不平衡检验(TDT)提示等位基因G优势传递给患者,传递:不传递(T:U)=62:41,P=0．0385。结论 PBX1基因可能为SLE的候选基因。     

PTPN22 C1858T与1型糖尿病相关性荟萃分析

利用荟萃分析评价PTPN22基因C1858T多态位点与1型糖尿病（T1DM）发病的相关性。资料来自Medline和中国生物医学文献数据库收录的文献，纳入涉及C1858T多态位点和T1DM相关性的病例对照或家系研究，应用RevMan4．2软件进行统计分析。相关文献未发现显著发表偏倚；在病例对照及家系研究中，T等位基因（P〈0．01，OR=1．87和P〈0．001，OR=1．66）均增加TIDM发病风险。PTPN22 C1858T位点与T1DM遗传易感性相关；该多态位点仅见于欧洲裔人群，在不同欧洲裔人群中，该位点遗传作用大小（OR）相似。     

ATⅡR-1基因A1166C多态性与缺血性脑卒中的关系

目的　了解 1型血管紧张素Ⅱ受体 (ATⅡR 1)基因A116 6C多态性与缺血性脑卒中的关系。方法　利用PCR和分子杂交技术对北京地区 2 94例缺血性脑卒中患者及 2 80例非缺血性脑卒中对照者进行ATⅡR 1基因A116 6C多态性检测和分析。结果　A116 6C多态性位点在两组人群中的分布均符合Hardy Weinberg遗传平衡定律 ,但该位点基因型频率及等位基因频率在两组中分布无差异。结论　本研究结果表明 ,ATⅡR 1基因A116 6C多态性不是中国人群缺血性脑卒中发病的遗传学危险因素     

胃动素基因多态性与先天性肥厚性幽门狭窄传递不平衡分析

目的探讨胃动素（motilin,MLN）基因第二外显子的多态性位点rs2281820[44C〉T]与先天性肥厚性幽门狭窄（congenital hypertrophic pyloric stenosis,CHPS）发病易感性的关联。方法对广州市第一人民医院住院的22个汉族核心家系（CHPS患者及父母双亲）采用PCR及测序方法进行基因分型,应用传递不平衡检验判断基因多态性与CHPS发病的关联。结果测序结果未发现新的突变位点;患儿及父母组内这两个多态性位点的Hardy-Weinberg平衡检验均P〉0.05,TDT检验提示多态性位点rs2281820[44C〉T]与CHPS发病无关（P=0.522）。结论胃动素基因的多态性位点rs2281820[44C〉T]与中国汉族人群CHPS发病无关。     

食管癌中DCC基因VNTR位点多态性研究

目的探讨DCC基因VNTR位点多态性在陕西人群中的分布规律及与食管癌的遗传易感性关系.方法利用PCR方法对陕西正常人群个体(56例),食管癌组织(鳞癌49例).食管癌癌旁组织(34例)的DCC基因VNTR位点多态性进行群体遗传学研究,并就该位点与食管癌的关系进行了关联分析.结果在陕西正常人群中DCC基因VNTR位点存在11种等位基因(A1～A11),扩增长度为167bp～210 bp,其等位基因频率介于0.009～0.188,其中以扩增长度为205 bp(A3.),201 bp(A4),185 bp(A7),177bp(A9)较为常见,分布符合HardyWeinberg遗传平衡定律;DCC基因VNTR位点在陕西正常人群中的多态信息量(PIC)为0.879,杂合度(H)为73.2%.在食管癌人群DCC基因VNTR位点中共检出10种等位基因,比正常人群少等位基因A2,其等位基因频率分布在0.01～0.25.癌组织与癌旁组织等位基因频率分布经比较无显著差异(X2=3.16,P＞0.05).食管癌人群DCC基因VNTR位点多态分布与正常人群有显著差异(P＜0.01).其中A5在食管癌人群中等位基因频率明显高于正常人群,而A7等位基因频率则明显低于正常人群,提示A5和A7可能是食管癌易感因素.结论推测DCC基因VNTR位点多态性的改变可能在食管癌的形成中起重要作用,该位点多态性与食管癌的遗传易感性相关.     

CD22基因多态性与中国南方汉族人群系统性红斑狼疮相关性研究

目的 探讨CD22基因T＞A位点(SNPrs2267574)与中国南方汉族人群系统性红斑狼疮(SLE)的遗传易感性及其表型间的相关性.方法 采用病例对照研究,收集215例病例和216例对照,应用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)技术进行基因分型,分析基因与疾病关联性以及表型相关性.结果 SLE患者组AT基因型的频率高于对照组(OR=1.68,95%CI:1.08～2.60,P=0.021);以T等位基因为参照,A等位基因的OR=1.58,95%CI:1.09～2.29,P=0.015;且A等位基因频率在抗SSA抗体阳性组高于抗SSA抗体阴性组(OR=3.69,95%CI:2.08～6.52,P＜0.01).结论 在中国南方汉族人群中,CD22基因T＞A位点与SLE具有相关性,抗SSA抗体的产生与A等位基因有关.     

BTLA基因多态性与慢性HBV感染家系的遗传易感性

目的:探讨中国汉族人群T、B淋巴细胞弱化因子(Band Tlymphocyte attenuator,BTLA)基因单核苷酸多态性(single nucleotide polymorphism,SNP)与慢性乙型肝炎病毒(hepatitis Bvirus,HBV)感染家系的遗传易感性.方法:采用SNaPshot技术检测核心家系中慢性HBV感染者及其家庭成员BTLA基因rs2633562和rs2952323 SNP位点的多态性,采用家系内关联性分析(family-based association test,FBAT)基因型、等位基因及单体型分布频率.结果:单位点S N P遗传关联性分析显示,BTLA基因rs2952323位点多态性与慢性HBV感染的遗传易感有显著的相关性,G/G基因型Z=2.731,P=0.006308,G等位基因在附加遗传模型中Z=2.689,P=0.0007174,隐性遗传模型中Z=2.731,P=0.006308.传统的传递不平衡检验(transmission/disequilibrium test,TDT)和同胞对传递不平衡检验(siblings disequilibrium test,SDT)分析显示无主要的优势等位基因A、C或G从杂合的父母传递给患病子女,P=1.000000,P=0.151590.FBAT单倍型分析结果显示rs2633562-A/rs2952323-G(70.0%)存在优势单倍型传递给患病子女或者患病同胞,在附加遗传模型Z=3.093,P=0.001979,隐性遗传模型中Z=2.825,P=0.004721.结论:BTLA基因位点多态性可能与家族聚集性慢性HBV感染的遗传易感性相关.     

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

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FCGR2A 131H/R、FCGR3A 158F/V、FCGR3BNA1/NA2和FCGR2B 232I/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FcγR基因多态性的分布差异.病例组与健康对照组比较采用x2检验或Fisher确切概率检验.结果 与健康对照组比较,FCGR2B 232I/I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;FCGR2B 232I/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:0.24～0.91)均明显减少.与颅外感染者比较,颅内感染者FCGR2A 131R/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FCGR2B 232I/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);FCGR2B 232I/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:0.24～0.79)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:0.14～0.68)均明显降低.结论 隐球菌病患者中的颅内感染与FCGR2A 131H/R、FCGR2B 232I/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.     

FcgammaRIIa polymorphism in Japanese patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an immune complex-mediated disease and organ damage is caused by the deposition of immune complex. Receptors which recognize the Fc portion of immunoglobulin G (FcgammaR) play a key role in the phagocytosis of immune complexes. As the gene encoding for FcgammaR of class IIa (FcgammaRIIa) has two allelic forms, H131 and R131, which differ in their affinity to IgG2, this polymorphism might have implications in handling immune complex. We studied the distribution of the FcgammaRIIa polymorphism in 90 Japanese patients with SLE. We also examined the association between FcgammaRIIa polymorphism and the disease activity of SLE and the histopathological findings of lupus nephritis. FcgammaRIIa polymorphism was determined by PCR and dot blot analysis. The allelic frequency of H131 in patients with SLE was significantly lower (H131/R131 = 0.44/0.56) than that of normal controls (H131/R131 = 0.62/0.38; P < 0.05). No significant association was observed between FcgammaRIIa polymorphism and the clinical parameters for the activity of SLE. There was no association between FcgammaRIIa polymorphism and the histological findings in lupus nephritis. The difference in the distribution of FcgammaRIIa alleles between patients with SLE and normal subjects indicates that this polymorphism is a candidate of susceptibility gene for SLE in Japanese.     

FcgammaRIIa/IIIa polymorphism and its association with clinical manifestations in Korean lupus patients

The aim of this study was to determine the distribution of the FcgammaRlla and FcgammaRIIIa polymorphisms and their association with clinical manifestations in Korean lupus patients. Three hundred SLE (systemic lupus erythematosus) patients (48 male, 252 female) meeting 1982 ACR criteria and 197 Korean disease-free controls were enrolled. Genotyping for FcgammaRlla 131 R/H and FcgammaRIIIa 176 F/V was performed by PCR of genomic DNA using allele-specific primers and the FcgammaRIIIa genotype was confirmed by direct sequencing of PCR product in some cases. There was significant skewing in the distribution of the three FcgammaRIIa genotypes between the SLE and the controls (P=0.002 for R/R131 vs R/H131 and H/H131, OR 2.5 (95% Cl 1.4-4.5), but not in FcgammaRIIIa genotypes. FcgammaRIIa-R allele was a significant predictor of lupus nephritis, as compared with SLE patients without nephritis (P=0.034 for R131 vs H131, OR 1.4 (95% Cl 1.03-1.9)), but proliferative nephritis (WHO class III and IV) was less common in patients with FcgammaRlla-R/R131 and in FcgammaRIIa-R allele. In 300 SLE patients, high binding allele combination H131/V176 was less common in SLE with nephritis than in SLE without nephritis. Hemolytic anemia was less common in R131/F176 allele combination among four FcgammaRIIa/FcgammaRIIIa allelic combinations. Male SLE patients showed a higher frequency of renal involvement, serositis, thrombocytopenia, malar rash and discoid rash than female SLE, and male SLE had a higher frequency of FcgammaRIIa-R/R131 or R131-allele than male controls, but FcgammaRIIa or FcgammaRIIIa genotypes had no association with renal involvement in male SLE patients. FcgammaRIIa-H/H131 showed a higher frequency of hemolytic anemia and less pulmonary complications in male SLE. Female SLE patients showed higher frequency of any hematologic abnormality, lymphopenia, anticardiolipin antibody (+) and anti-Ro antibody (+) than male SLE, and had earlier onset of first symptoms. There was no skewing in FcgammaRIIa or FcgammaRIIIa genotypes between female SLE and female controls, but FcgammaRIIa-R131 allele showed skewing between female SLE with nephritis and female SLE without nephritis. The age at onset of thrombocytopenia was earlier in FcgammaRIIa R/R131 among three FcgammaRIIa genotypes, and serositis in FcgammaRIIIa-F/F176 among three FcgammaRIIIa genotypes. FcgammaRIIa-R131 homozygote was a major predisposing factor to the development of SLE and FcgammaRIIa-RI31 homozygote and R131 allele were a predisposing factor, and H131/V176 was a protective allele combination in lupus nephritis. In contrast to other ethnic patients, in our study cohort, clinical manifestation was different between male and female, and FcgammaRIIa and FcgammaRIIIa showed somewhat different clinical associations between the genders.     

Clinical and genetic risk factors for pneumonia in systemic lupus erythematosus

OBJECTIVE: To define the contribution of polymorphisms in genes encoding tumor necrosis factor (TNF), mannose-binding lectin (MBL), and Fcgamma receptor IIa (FCGR2A) as well as clinical factors, to the development of pneumonia in patients with systemic lupus erythematosus (SLE). METHODS: We studied 282 SLE patients from a multiethnic cohort. Pneumonia events and clinical risk factors for pneumonia were identified through medical record review. Genotyping was performed for MBL (+223, +230, and +239), TNF (-308, -238, and +488), and FCGR2A (-131H/R) polymorphisms. Univariate analyses were performed to identify clinical and genetic risk factors for pneumonia. Covariates for multivariate analysis included sex, ethnicity, treatment with immunomodulators, and leukopenia. RESULTS: Forty-two patients (15%) had at least 1 episode of pneumonia. Polymorphism of the TNF gene, particularly the -238A allele and a related haplotype, revealed the most striking and consistent association with pneumonia in univariate analyses. Results of multivariate analyses indicated an odds ratio (OR) for the TNF -238A allele of 3.5 (P = 0.007) and an OR for the related haplotype of 5.4 (P = 0.001). Male sex, treatment with immunomodulators, and leukopenia also influenced the risk of pneumonia. CONCLUSION: These findings suggest that specific TNF variants may identify SLE patients who are at particularly high risk of developing pneumonia. Given the prevalence and excessive morbidity associated with pneumonia in SLE, these findings have clinical relevance and provide insight into the pathogenesis.     

Fcgamma receptor gene polymorphisms in Japanese patients with systemic lupus erythematosus: contribution of FCGR2B to genetic susceptibility

OBJECTIVE: Human low-affinity Fcgamma receptors (FcgammaR) constitute a clustered gene family located on chromosome 1q23, that consists of FcgammaRIIA, IIB, IIC, IIIA, and IIIB genes. FcgammaRIIB is unique in its ability to transmit inhibitory signals, and recent animal studies demonstrated a role for FcgammaRIIB deficiency in the development of autoimmunity. Genetic variants of FcgammaRIIA, IIIA, and IIIB and their association with systemic lupus erythematosus (SLE) have been extensively studied in various populations, but the results were inconsistent. To examine the possibility that another susceptibility gene of primary significance exists within the FcgammaR region, we screened for polymorphisms of the human FCGR2B gene, and examined whether these polymorphisms are associated with SLE. METHODS: Variation screening of FCGR2B was performed by direct sequencing and polymerase chain reaction (PCR)-single-strand conformation polymorphism methods using complementary DNA samples. Genotyping of the detected polymorphism was done using genomic DNA, with a specific genotyping system based on nested PCR and hybridization probing. Association with SLE was analyzed in 193 Japanese patients with SLE and 303 healthy individuals. In addition, the same groups of patients and controls were genotyped for the previously known polymorphisms of FCGR2A, FCGR3A, and FCGR3B. RESULTS: We detected a single-nucleotide polymorphism in FCGR2B, (c.695T>C), coding for a nonsynonymous substitution, Ile232Thr (I232T), within the transmembrane domain. The frequency of the 232T/T genotype was significantly increased in SLE patients compared with healthy individuals. When the same patients and controls were also genotyped for FCGR2A-131R/H, FCGR3A-176V/F, and FCGR3B-NA1/2 polymorphisms, FCGR3A-176F/F showed significant association. Two-locus analyses suggested that both FCGR2B and FCGR3A may contribute to SLE susceptibility, while the previously reported association of FCGR3B was considered to be secondary and derived from strong linkage disequilibrium with FCGR2B. CONCLUSION: These results demonstrate the association of a new polymorphism of FCGR2B (I232T) with susceptibility to SLE in the Japanese.     

Independent association of HLA-DR and FCgamma receptor polymorphisms in Korean patients with systemic lupus erythematosus

OBJECTIVES: To determine the distribution of HLA-DR type and FcgammaRIIa/IIIa polymorphisms, and to analyse the combined effects of these genes for susceptibility in Korean systemic lupus erythematosus (SLE) patients. METHODS: A total of 299 SLE patients meeting 1982 ACR criteria and 144 Korean disease-free controls were enrolled. Genotyping for the FcgammaRIIa 131 R/H and FcgammaRIIIa 176 F/V was performed by polymerase chain reaction (PCR) of genomic DNA using allele-specific primers. HLA-DRB1 typing was performed by the PCR-SSOP method. RESULTS: There was significant skewing in the distribution of the three FcgammaRIIa genotypes between the SLE patients and the controls [P = 0.002 for R/R131 vs R/H131 and H/H131, relative risk (RR) 2.6 (95% CI 1.3-5.2)], but not in FcgammaRIIIa genotypes. HLA-DRB1*15 allele was significantly more prevalent among SLE patients than the control population [P < 0.02, RR = 1.7 (1.1-2.6)]. HLA-DRB1 genotypes or allele frequencies of the SLE patients with nephritis did not differ significantly from those of the SLE patients without nephritis. We analysed the combined effects of the two candidate genes on SLE susceptibility. HLA-DRB1*15 allele was a significant predictor of SLE in individuals who were not homozygous for FcgammaRIIa-R/R131 [RR = 2.1 (1.2-3.7), P < 0.008], and the FcgammaRIIa-R/R131 genotype vice versa [RR = 5.3 (1.9-15.4), P < 0.001]. However, an additive or synergistic effect of both susceptible genes on relative risk for SLE was not evident. CONCLUSIONS: Our results suggest that FcgammaRIIa-R/R131 homozygote and HLA-DRB1*15 allele are independent risk factors in Korean SLE patients without additive or synergistic effects.     

FCGR3A gene polymorphisms may correlate with response to frontline R-CHOP therapy for diffuse large B-cell lymphoma

The precise mechanism of rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (R-CHOP) therapy in diffuse large B-cell lymphoma (DLBCL) is not fully elucidated. Besides overcoming bcl-2-mediated chemoresistance, antibody-dependent cellular cytotoxicity (ADCC), which is activated by effector cells via immunoglobulin G (IgG) fragment C receptors (FcRs), was also proposed as a mechanism of rituximab. The current study evaluated the impact of FcR polymorphism on the response to R-CHOP therapy for DLBCL with the basis that FcR polymorphism can affect rituximab's affinity for ADCC effector cells. The FCGR3A and FCGR2A gene polymorphisms were determined in DLBCL patients receiving R-CHOP (n = 113) compared with CHOP therapy (n = 85). The FCGR3A valine (V) allele was significantly correlated with a higher complete response rate to R-CHOP compared with the phenylalanine (F) allele (88% in V/V vs 79% in V/F vs 50% in F/F; P = .002), while no difference was found between FCGR2A polymorphisms. In addition, V/V allele was associated with faster achievement of response than other alleles. The impact of the FCGR3A gene polymorphism on response rate was not noted in the CHOP group. In terms of overall or event-free survival, no difference was found according to FCGR3A or FCGR2A alleles. The FCGR3A single nucleotide polymorphism (SNP) is predictive of response to R-CHOP, but does not correlate with survival in patients with DLBCL.     

Overrepresentation of the Fcgamma receptor type IIA R131/R131 genotype in caucasoid systemic lupus erythematosus patients with autoantibodies to C1q and glomerulonephritis.

OBJECTIVE: To test the hypothesis that there is an association between the Fcgamma receptor type IIA (FcgammaRIIA)-H/R131 polymorphism and autoantibodies to the collagenous region (CLR) of C1q in patients with systemic lupus erythematosus (SLE). METHODS: One hundred ninety-five Caucasoid lupus patients were studied. Anti-C1q(CLR) antibodies in serum were measured by enzyme-linked immunosorbent assay (ELISA) and FcgammaRIIA genotype analysis was performed by polymerase chain reaction. Immunoglobulin subclass of the autoantibodies was measured by ELISA. RESULTS: Fifty-six patients were anti-C1q antibody positive, and Ig subclass analysis indicated a predominance of IgG2 anti-C1q antibodies. Analysis of the SLE population as a whole revealed no significant difference in the allele frequencies of R131 and H131 compared with controls. There was, however, a significantly increased frequency of the R131 allele both in the anti-C1q-positive subgroup of patients (chi2 = 7.66, P<0.01) and in the 71 patients with nephritis (chi2 = 7.76, P< 0.01), compared with controls. CONCLUSION: FcgammaRIIA-R131 constitutes a heritable susceptibility factor for the development of SLE with manifestations in the kidney in Caucasoid patients. The close associations demonstrated between this FcgammaRII variant, antibodies to C1q(CLR), and glomerulonephritis may be due to a failure of clearance of the potentially pathogenic IgG2 autoantibody.     

FC gamma receptor polymorphisms in patients with immune thrombocytopenia

Introduction: Immune thrombocytopenia (ITP) is an autoimmune blood disease of unknown etiology. The aim of our study was to investigate a possible role of FCGR2A and FCGR3A polymorphisms in the development of primary ITP.

Methods: We analyzed 125 adult patients with ITP and 120 healthy controls. Genotyping was performed by using PCR-RFLP methods.

Results: Our results showed significantly higher frequency of high-affinity FCGR3A-158V allele in patients with ITP compared with control subjects (47.2% versus 37.5%; p?=?0.037). We did not find significant differences in the genotype distribution or allele frequencies for FCGR2A-131H/R between patients and controls, p?=?0.652 and p?=?0.478. In the groups of patients with unresponsive and responsive ITP we found significantly different genotype distribution and allele frequencies for FCGR3A, p?=?0.036 and p?=?0.008 respectively. There was no significant difference in genotype and allele frequencies for FCGR2A between these two groups of patients. Our results confirmed that the combination of high-affinity FCGR2A-131H and FCGR3A-158V allele was more common in patients with ITP than in controls (55% versus 40%; p?=?0.024).

Conclusion: Our results suggest possible role of FCGR3A polymorphism in the etiology, development and clinical outcome of ITP, but larger prospective studies are needed to confirm these results.     

Associations between PTPRC rs10919563 A/G and FCGR2A R131H polymorphisms and responsiveness to TNF blockers in rheumatoid arthritis: a meta-analysis

We aimed to investigate whether the PTPRC rs10919563 A/G and Fc gamma receptor 2A (FCGR2A) R131H polymorphisms can predict the response to anti-TNF therapy in rheumatoid arthritis (RA) patients. We conducted a meta-analysis of studies on the association between the PTPRC rs10919563 A/G or the FCGR2A R131H polymorphism and responsiveness to anti-TNF therapy in RA patients. Eighteen studies (twelve on PTPRC and six on FCGR2A) from eight articles involving 3058 patients were considered in this meta-analysis. The meta-analysis showed a significant association between the PTPRC rs10919563 A allele and response to TNF-α blockers in RA. The OR of the PTPRC A allele was significantly lower in responders (OR = 0.584, 95 % CI = 0.409–0.835, P = 0.003). Meta-analysis revealed no association between the FCGR2A HH + HR genotype and responsiveness to TNF blockers in all study subjects (OR = 0.762, 95 % CI = 0.543–1.068, P = 0.115). However, stratification by TNF inhibitor type showed that the FCGR2A HH + HR genotype was associated with responsiveness to adalimumab (OR = 0.591, 95 % CI = 0.369–0.947, P = 0.029), but not infliximab and etanercept (OR = 0.929, 95 % CI = 0.354–2.440, P = 0.881; OR = 0.804, 95 % CI = 0.293–2.207, P = 0.673). The PTPRC rs10919563 A allele shows a poor response to anti-TNF therapy, and the FCGR2A HH + HR genotype shows a poor response to adalimumab for RA. Genotyping for these polymorphisms may be useful for predicting the response to TNF-α blockers with respect to personalized medicine.