Correlations of FCGR2A 131R/H and FCGR3A 158V/F Polymorphisms with the Susceptibility of Peri-implantitis in Chinese Han Population.

The purpose of the study is to investigate the relationship of peri-implantitis (PI) with FCGR2A and FCGR3A gene polymorphisms. One hundred and forty-four patients with PI and 136 patients without PI infection were selected. Gingival crevicular fluid samples were collected from the two groups. The FCGR2A and FCGR3A polymorphism in the two groups were measured. All volunteers were evaluated for periodontal status. The effect of polymorphisms on PI susceptibility was investigated by chi-square analysis and logistic regression. The frequency of FCGR2A rs1801274 GG genotype of PI group was higher than that of the control group, while the GA and AA genotype carriers were less in PI group. After adjusting for other clinical indicators, rs1801274 GA genotype, AA genotype, and the A allele were still negatively correlated with the onset of PI. FCGR3A rs396991 polymorphism was not associated with PI. FCGR2A rs1801274 polymorphism was significantly associated with PI in the Chinese Han population, and GG genotype might be a genetic risk factor for PI.

Immunoglobulin genes and severity of COVID-19.

There is tremendous interindividual and interracial variability in the outcome of SARS-CoV-2 infection, suggesting the involvement of host genetic factors. Here, we investigated whether IgG allotypes GM (γ marker) 3 and GM 17, genetic markers of IgG1, contributed to the severity of COVID-19. IgG1 plays a pivotal role in response against SARS-CoV-2 infection. We also investigated whether these GM alleles synergistically/epistatically with IGHG3 and FCGR2A alleles-which have been previously implicated in COVID-19-modulated the extent of COVID-19 severity. The study population consisted of 316 COVID-19 patients who needed treatment in the intensive care unit of Hospital Universitario Central de Asturias. All individuals were genotyped for GM 3/17, IGHG3 hinge length, and FCGR2A rs1801274 A/G polymorphisms. Among the 316 critical patients, there were 86 deaths. The risk of death among critical patients was significantly higher in subjects with GM 17 (IgG1) and short hinge length (IgG3). GM 17-carriers were at almost three-fold higher risk of death than non-carriers (p < 0.001; OR = 2.86, CI 1.58-5.16). Subjects with short hinge length of IgG3 had a two-fold higher risk of death than those with medium hinge length (p = 0.01; OR = 2.16, CI 1.19-3.90). GM 3/3 and IGHG3 (MM) genotypes were less frequent among death vs. survivors (9% vs 36%, p < 0.001) and associated with protective effect (OR = 0.18, 95% CI = 0.08-0.39). This is the first report implicating IgG1 allotypes in COVID-19-spurred death. It needs to be replicated in an independent study population.

Regulatory mechanism of FCGR2A in macrophage polarization and its effects on intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) poses a significant health burden, necessitating a deeper understanding of its molecular underpinnings. Transcriptomic analysis reveals 485 differentially expressed genes (DEGs) associated with IDD, underscoring the importance of immune regulation. Weighted gene co-expression network analysis (WGCNA) identifies a yellow module strongly correlated with IDD, intersecting with 197 DEGs. Protein-protein interaction (PPI) analysis identifies ITGAX, MMP9 and FCGR2A as hub genes, predominantly expressed in macrophages. Functional validation through in vitro and in vivo experiments demonstrates the pivotal role of FCGR2A in macrophage polarization and IDD progression. Mechanistically, FCGR2A knockdown suppresses M1 macrophage polarization and NF-κB phosphorylation while enhancing M2 polarization and STAT3 activation, leading to ameliorated IDD in animal models. This study sheds light on the regulatory function of FCGR2A in macrophage polarization, offering novel insights for IDD intervention strategies. KEY POINTS: This study unveils the role of FCGR2A in intervertebral disc (IVD) degeneration (IDD). FCGR2A knockdown mitigates IDD in cellular and animal models. Single-cell RNA-sequencing uncovers diverse macrophage subpopulations in degenerated IVDs. This study reveals the molecular mechanism of FCGR2A in regulating macrophage polarization. This study confirms the role of the NF-κB/STAT3 pathway in regulating macrophage polarization in IDD.

A Non-Coding Fc Gamma Receptor Cis-Regulatory Variant within the 1q23 Gene Cluster Is Associated with Plasmodium falciparum Infection in Children Residing in Burkina Faso.

Antibodies play a crucial role in activating protective immunity against malaria by interacting with Fc-gamma receptors (FcγRs). Genetic variations in genes encoding FcγRs can affect immune cell responses to the parasite. In this study, our aim was to investigate whether non-coding variants that regulate FcγR expression could influence the prevalence of Plasmodium falciparum infection. Through bioinformatics approaches, we selected expression quantitative trait loci (eQTL) for FCGR2A, FCGR2B, FCGR2C, FCGR3A, and FCGR3B genes encoding FcγRs (FCGR), in whole blood. We prioritized two regulatory variants, rs2099684 and rs1771575, located in open genomic regions. These variants were identified using RegVar, ImmuNexUT, and transcription factor annotations specific to immune cells. In addition to these, we genotyped the coding variants FCGR2A/rs1801274 and FCGR2B/rs1050501 in 234 individuals from a malaria-endemic area in Burkina Faso. We conducted age and family-based analyses to evaluate associations with the prevalence of malarial infection in both children and adults. The analysis revealed that the regulatory rs1771575-CC genotype was predicted to influence FCGR2B/FCGR2C/FCGR3A transcripts in immune cells and was the sole variant associated with a higher prevalence of malarial infection in children. In conclusion, this study identifies the rs1771575 cis-regulatory variant affecting several FcγRs in myeloid and neutrophil cells and associates it with the inter-individual capacity of children living in Burkina Faso to control malarial infection.

The Relationship between COVID-19 Severity in Children and Immunoregulatory Gene Polymorphism.

Coronavirus disease (COVID-19) and its outcomes remain one of the most challenging problems today. COVID-19 in children could be asymptomatic, but can result in a fatal outcome; therefore, predictions of the disease severity are important. The goal was to investigate the human genetic factors that could be associated with COVID-19 severity in children. Single-nucleotide polymorphisms of the following genes were studied: ACE2 (rs2074192), IFNAR2 (rs2236757), TYK2 (rs2304256), OAS1 (rs10774671), OAS3 (rs10735079), CD40 (rs4813003), FCGR2A (rs1801274) and CASP3 (rs113420705). In the case-control study were 30 children with mild or moderate course of the disease; 30 with severe COVID-19 symptoms and multisystem inflammatory syndrome in children (MIS-C) and 15 who were healthy, and who did not have SARS-CoV-2 (PCR negative, Ig G negative). The study revealed that ACE2 rs2074192 (allele T), IFNAR2 rs2236757 (allele A), OAS1 rs10774671 (allele A), CD40 rs4813003 (allele C), CASP3 rs113420705 (allele C) and male sex contribute to severe COVID-19 course and MIS-C in 85.6% of cases. The World Health Organization reported that new SARS-CoV-2 variants may cause previously unseen symptoms in children. Although the study has limitations due to cohort size, the findings can help provide a better understanding of SARS-CoV-2 infection and proactive pediatric patient management.

The FCGR2A Is Associated with the Presence of Atherosclerotic Plaques in the Carotid Arteries-A Case-Control Study.

BACKGROUND: Atherosclerotic plaques in carotid arteries (APCA) are a prevalent condition with severe potential complications. Studies continuously search for innovative biomarkers for APCA, including those participating in cellular metabolic processes, cell adhesion, immune response, and complement activation. This study aimed to assess the relationship between APCA presence and a broad range of cardiometabolic biomarkers in the general population. METHODS: The study group consisted of consecutive participants of the population study Bialystok PLUS. The proximity extension assay (PEA) technique from the Olink Laboratory (Uppsala, Sweden) was used to measure the levels of 92 cardiometabolic biomarkers. RESULTS: The study comprised 693 participants (mean age 48.78 ± 15.27 years, 43.4% males, N = 301). APCA was identified in 46.2% of the participants (N = 320). Of the 92 biomarkers that were investigated, 54 were found to be significantly linked to the diagnosis of APCA. After adjusting for the traditional risk factors for atherosclerosis in multivariate analysis, the only biomarker that remained significantly associated with APCA was FCGR2A. CONCLUSION: In the general population, the prevalence of APCA is very high. A range of biomarkers are linked with APCA. Nonetheless, the majority of these associations are explained by traditional risk factors for atherosclerosis. The only biomarker that was independently associated with APCA was the FCGR2A.

Association between the functional FCGR3A F158V and FCGR2A R131H polymorphisms and responsiveness to biologics in rheumatoid arthritis patients: A meta-analysis.

OBJECTIVES: This study aimed to investigate the association between functional Fc gamma receptor 3A (FCGR3A) V158F and FCGR2A R131H polymorphisms and biologic therapy in rheumatoid arthritis (RA) patients. METHODS: We searched Medline, Embase, and Cochran databases for available articles. This study is a meta-analysis of the association between the FCGR3A V158F and FCGR2A R131H polymorphisms and their responsiveness to biologics in RA patients. RESULTS: Seventeen studies involving RA patients with FCGR3A V158F (n = 1884) and FCGR2A R131H (n = 1118) polymorphisms were considered. This meta-analysis showed that the FCGR3A V allele was associated with responsiveness to rituximab (odds ratio [OR] = 1.431, 95% CI = 1.081-1.894, P = 0.012), but not with tumor necrosis factor (TNF) blockers, tocilizumab, or abatacept. A significant association was also found between the FCGR3A V158F polymorphism and responsiveness to biologics using the dominant-recessive model. Additionally, the FCGR3A V158F polymorphism was associated with responsiveness to TNF blockers in the homozygous contrast model. Meta-analysis revealed an association between the FCGR2A RR + RH genotype and responsiveness to biologics (OR = 1.385, 95% CI = 1.007-1.904, P = 0.045). CONCLUSIONS: This meta-analysis demonstrates that FCGR3A V allele carriers show better responsiveness to rituximab, and FCGR2A R allele carriers may show a better response to biologics in RA treatment. Genotyping of these polymorphisms could be a useful tool to find associations with the responsiveness of personalized medicine to biologics.

Modeling of clinical phenotypes in systemic lupus erythematosus based on the platelet transcriptome and FCGR2a genotype.

BACKGROUND: The clinical heterogeneity of SLE with its complex pathogenesis remains challenging as we strive to provide optimal management. The contribution of platelets to endovascular homeostasis, inflammation and immune regulation highlights their potential importance in SLE. Prior work from our group showed that the Fcγ receptor type IIa (FcγRIIa)-R/H131 biallelic polymorphism is associated with increased platelet activity and cardiovascular risk in SLE. The study was initiated to investigate the platelet transcriptome in patients with SLE and evaluate its association across FcγRIIa genotypes and distinct clinical features. METHODS: Fifty-one patients fulfilling established criteria for SLE (mean age = 41.1 ± 12.3, 100% female, 45% Hispanic, 24% black, 22% Asian, 51% white, mean SLEDAI = 4.4 ± 4.2 at baseline) were enrolled and compared with 18 demographically matched control samples. The FCGR2a receptor was genotyped for each sample, and RNA-seq was performed on isolated, leukocyte-depleted platelets. Transcriptomic data were used to create a modular landscape to explore the differences between SLE patients and controls and various clinical parameters in the context of FCGR2a genotypes. RESULTS: There were 2290 differentially expressed genes enriched for pathways involved in interferon signaling, immune activation, and coagulation when comparing SLE samples vs controls. When analyzing patients with proteinuria, modules associated with oxidative phosphorylation and platelet activity were unexpectedly decreased. Furthermore, genes that were increased in SLE and in patients with proteinuria were enriched for immune effector processes, while genes increased in SLE but decreased in proteinuria were enriched for coagulation and cell adhesion. A low-binding FCG2Ra allele (R131) was associated with decreases in FCR activation, which further correlated with increases in platelet and immune activation pathways. Finally, we were able to create a transcriptomic signature of clinically active disease that performed significantly well in discerning SLE patients with active clinical disease form those with inactive clinical disease. CONCLUSIONS: In aggregate, these data demonstrate the platelet transcriptome provides insight into lupus pathogenesis and disease activity, and shows potential use as means of assessing this complex disease using a liquid biopsy.

The FCGR2A rs1801274 polymorphism was associated with the risk of death among COVID-19 patients.

Polymorphisms of Fcγ receptors have been associated with variable responses to infections. We determined the association of functional polymorphisms rs1801274 in the FCGR2A and rs396991 in the FCGR3A with COVID-19 severity. This study involved 453 patients with severe COVID-19, in which the FCGR2A rs1801274 G-allele (131-Arg) was significantly associated with death (p = 0.02, OR = 1.47). This effect was independent of age and increased IL6 and D-Dimer levels. This study suggests that the FCGR2A gene might be associated with the risk of death among COVID-19 patients. Our study has several limitations, mainly the limited number of patients and the inclusion of a single population. It is thus necessary to confirm this result in larger cohorts from different populations.

A data-driven methodology towards evaluating the potential of drug repurposing hypotheses.

Drug repurposing has become a widely used strategy to accelerate the process of finding treatments. While classical de novo drug development involves high costs, risks, and time-consuming paths, drug repurposing allows to reuse already-existing and approved drugs for new indications. Numerous research has been carried out in this field, both in vitro and in silico. Computational drug repurposing methods make use of modern heterogeneous biomedical data to identify and prioritize new indications for old drugs. In the current paper, we present a new complete methodology to evaluate new potentially repurposable drugs based on disease-gene and disease-phenotype associations, identifying significant differences between repurposing and non-repurposing data. We have collected a set of known successful drug repurposing case studies from the literature and we have analysed their dissimilarities with other biomedical data not necessarily participating in repurposing processes. The information used has been obtained from the DISNET platform. We have performed three analyses (at the genetical, phenotypical, and categorization levels), to conclude that there is a statistically significant difference between actual repurposing-related information and non-repurposing data. The insights obtained could be relevant when suggesting new potential drug repurposing hypotheses.

Influence of the FCGR2A rs1801274 and FCGR3A rs396991 Polymorphisms on Response to Abatacept in Patients with Rheumatoid Arthritis.

Abatacept (ABA) is an immunosuppressant indicated for treatment of rheumatoid arthritis (RA). Effectiveness might be influenced by clinical RA variants and single-nucleotide polymorphisms (SNPs) in genes encoding protein FCGR2A (His131Arg) and FCGR3A (Phe158Val) involved in pharmacokinetics of ABA. An observational cohort study was conducted in 120 RA Caucasian patients treated with ABA for 6 and 12 months. Patients with the FCGR2A rs1801274-AA genotype (FCGR2A-p.131His) showed a better EULAR response (OR = 2.43; 95% CI = 1.01-5.92) at 12 months and low disease activity (LDA) at 6 months (OR = 3.16; 95% CI = 1.19-8.66) and 12 months (OR = 6.62; 95% CI = 1.25-46.89) of treatment with ABA. A tendency was observed towards an association between the FCGR3A rs396991-A allele (FCGR3A-p.158Phe) and better therapeutic response to ABA after 12 months of treatment (p = 0.078). Moreover, we found a significant association between the low-affinity FCGR2A/FCGR3A haplotypes variable and LDA after 12 months of ABA treatment (OR = 1.59; 95% CI = 1.01-2.58). The clinical variables associated with better response to ABA were lower age at starting ABA (OR = 1.06; 95% CI = 1.02-1.11) and greater duration of ABA treatment (OR = 1.02; 95% CI = 1.01-1.04), lower duration of previous biological therapies (OR = 0.99; 95% CI = 0.98-0.99), non-administration of concomitant disease-modifying antirheumatic drugs (DMARDs) (OR = 24.53; 95% CI = 3.46-523.80), non-use of concomitant glucocorticoids (OR = 0.12; 95% CI = 0.02-0.47), monotherapy (OR = 19.22; 95% CI = 2.05-343.00), lower initial patient's visual analogue scale (PVAS) value (OR = 0.95; 95% CI = 0.92-0.97), and lower baseline ESR (OR = 0.92; 95% CI = 0.87-0.97). This study showed that high-affinity FCGR2A-p.131His variant, low-affinity FCGR3A-p.158Phe variant, and combined use of FCGR2A/FCGR3A genetic variations could affect ABA effectiveness. Further studies will be required to confirm these results.

Adjuvant herbal therapy for targeting susceptibility genes to Kawasaki disease: An overview of epidemiology, pathogenesis, diagnosis and pharmacological treatment of Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is a self-limiting acute systemic vasculitis occur mainly in infants and young children under 5 years old. Although the use of acetylsalicylic acid (AAS) in combination with intravenous immunoglobulin (IVIG) remains the standard therapy to KD, the etiology, genetic susceptibility genes and pathogenic factors of KD are still un-elucidated. PURPOSE: Current obstacles in the treatment of KD include the lack of standard clinical and genetic markers for early diagnosis, possible severe side effect of AAS (Reye's syndrome), and the refractory KD cases with resistance to IVIG therapy, therefore, this review has focused on introducing the current advances in the identification of genetic susceptibility genes, environmental factors, diagnostic markers and adjuvant pharmacological intervention for KD. RESULTS: With an overall update in the development of KD from different aspects, our current bioinformatics data has suggested CASP3, CD40 and TLR4 as the possible pathogenic factors or diagnostic markers of KD. Besides, a list of herbal medicines which may work as the adjunct therapy for KD via targeting different proposed molecular targets of KD have also been summarized. CONCLUSION: With the aid of modern pharmacological research and technology, it is anticipated that novel therapeutic remedies, especially active herbal chemicals targeting precise clinical markers of KD could be developed for accurate diagnosis and treatment of the disease.

Association between FCGR2A rs1801274 and MUC5B rs35705950 variations and pneumonia susceptibility.

BACKGROUND: Herein, we collected currently published data to comprehensively evaluate the impact of the FCGR2A (Fc fragment of IgG receptor IIa) rs1801274 and MUC5B (mucin 5B, oligomeric mucus/gel-forming) rs35705950 variations on susceptibility to pneumonia diseases. METHODS: We retrieved case-control studies from three online databases and applied the statistical approach of meta-analysis for a series of pooling analyses. RESULTS: A total of fourteen case-control studies were included for FCGR2A rs1801274; while thirty-one case-control studies were included for MUC5B rs35705950. No significant difference between pneumonia cases and controls for FCGR2A rs1801274 was found. However, MUC5B rs35705950 was significantly associated with pneumonia susceptibility in the whole population under the genetic models of allelic T vs. G [OR (odds ratio) =3.78], carrier T vs. G (OR = 3.31), TT vs. GG (OR = 13.66), GT vs. GG (OR = 4.78), GT + TT vs. GG (OR = 5.05), and TT vs. GG + GT (OR = 6.47) (all P < 0.001, Bonferroni-adjusted P < 0.006; false discovery rate-adjusted P < 0.0010). Furthermore, we observed a similar positive result for subgroup analyses of "Caucasian", "Asian", "population-based control", and "idiopathic pulmonary fibrosis". CONCLUSIONS: MUC5B rs35705950, but not FCGR2A rs1801274, increases susceptibility to clinical pneumonia, especially to idiopathic pulmonary fibrosis, in both the Caucasian and Asian populations.

Identification of complement-related host genetic risk factors associated with influenza A(H1N1)pdm09 outcome: challenges ahead.

Influenza remains an important threat for human health, despite the extensive study of influenza viruses and the production of effective vaccines. In contrast to virus genetics determinants, host genetic factors with clinical impact remained unexplored until recently. The association between three single nucleotide polymorphisms (SNPs) and influenza outcome in a European population was investigated in the present study. All samples were collected during the influenza A(H1N1)pdm09 post-pandemic period 2010-11 and a sufficient number of severe and fatal cases was included. Host genomic DNA was isolated from pharyngeal samples of 110 patients from northern Greece with severe (n = 59) or mild (n = 51) influenza A(H1N1)pdm09 disease, at baseline, and the genotype of CD55 rs2564978, C1QBP rs3786054 and FCGR2A rs1801274 SNPs was investigated. Our findings suggest a relationship between the two complement-related SNPs, namely, the rare TT genotype of CD55 and the rare AA genotype of C1QBP with increased death risk. No significant differences were observed for FCGR2A genotypes neither with fatality nor disease severity. Additional large-scale genetic association studies are necessary for the identification of reliable host genetic risk factors associated with influenza A(H1N1)pdm09 outcome. Prophylactic intervention of additional high-risk populations, according to their genetic profile, will be a key achievement for the fight against influenza viruses.

FCGR2A/FCGR3A Gene Polymorphisms and Clinical Variables as Predictors of Response to Tocilizumab and Rituximab in Patients With Rheumatoid Arthritis.

We evaluated the influence of clinical, biochemical, and genetic factors on response in 142 patients diagnosed with rheumatoid arthritis, of whom 87 patients were treated with tocilizumab (61.26%) and 55 patients were treated with rituximab (38.7%;) according to the variables European League Against Rheumatism (EULAR) response, remission, low disease activity, and improvement in Disease Activity Score, 28 joints (DAS28) at 6, 12, and 18 months. A retrospective prospective cohort study was conducted. Patients carrying the FCGR3A rs396991-TT genotype treated with tocilizumab showed higher EULAR response (OR, 5.075; 95%CI, 1.20-21.33; P = .027) at 12 months, those who were naive for biological disease-modifying antirheumatic drugs (bDMARDs) at the beginning of treatment showed satisfactory EULAR response, higher remission, and greater improvement in DAS28 at 6 months. Younger age at start of tocilizumab treatment was associated with satisfactory EULAR response at 18 months and greater remission at 6 and 18 months. Subcutaneous tocilizumab administration was associated with higher remission at 6 months and improved low disease activity rate at 12 months. In patients treated with rituximab, carriers of the FCGR2A rs1801274-TT genotype had higher EULAR response at 6 months (OR, 4.861; 95%CI, 1.11-21.12; P = .035), 12 months (OR, 4.667; p = 0.066, 95%CI, 0.90-24.12; P = .066), and 18 months (OR, 2.487; 95%CI, 0.35-17.31; P = .357), higher remission (OR: 10.625; p = 0.044, CI95% : 1.07, 105.47) at 6 months, and greater improvement in DAS28 at 12 months (B = 0.782; 95%CI, -0.15 to 1.71; P = .098) and 18 months (B = 1.414; 95%CI, 0.19-2.63; P = .025). The FCGR3A rs396991-G allele was associated with improved low disease activity rate (OR, 4.904; 95%CI, 0.84-28.48; P = .077) and greater improvement in DAS28 (B = -1.083; 95%CI, -1.98 to -0.18; P = .021) at 18 months. Patients with a lower number of previous biological therapies had higher remission at 12 months. We suggest that the FCGR3A rs396991-TT genotype, higher baseline value of DAS28, subcutaneous tocilizumab administration, younger age at the beginning of treatment, and being bDMARD naive are associated with better response to tocilizumab. In patients treated with rituximab, we found better response in those patients with the FCGR2A rs1801274-TT genotype, the FCGR3A rs396991-G allele, and lower number of previous biological therapies.

Fc-gamma receptor polymorphisms, cetuximab therapy, and overall survival in the CCTG CO.20 trial of metastatic colorectal cancer.

BACKGROUND: Two germ line Fc-γ receptor (FCGR) polymorphisms, rs1801274 [FCGR2A; His(H)131Arg(R)] and rs396991 [FCGR3A; Phe(F)158Val(V)], produce altered proteins through amino acid substitutions. We previously reported that the FCGR2A H/H genotype was associated with longer overall survival (OS) in cetuximab-treated chemotherapy-refractory patients with metastatic colorectal cancer. Here, we aimed to replicate and extend this finding in the Canadian Clinical Trials Group CO.20 trial. METHODS: After germ line DNA genotyping, polymorphic relationships with survival were assessed using log-rank tests and hazard ratios (HR) from Cox proportional hazard models, adjusting for known prognostic factors. The dominant genetic inheritance model was used for the main analysis. RESULTS: Of 592 wild-type KRAS patients treated with cetuximab, those with the FCGR2A H/H genotype (n = 165, 28%) had improved OS (HR: 0.66, P < 0.001; median absolute benefit, 1.3 months) compared to those with R/- genotype (n = 427, 72%). Patients with H/R had intermediate results under a codominant genetic inheritance model (HR: 0.72, P = 0.003). No significant associations were found between FCGR3A genotype and OS. In an exploratory analysis, patients with the combination of FCGR2A H/H + FCGR3A F/F genotype had significantly better OS (HR: 0.33, P = 0.003; median absolute benefit, 12.5 months) than patients with the combination of double-variant R/R + V/V genotype. Progression-free survival results were similar to OS. Toxicity rates were not associated with either polymorphism. CONCLUSIONS: The FCGR2A genotype was associated with efficacy but not with toxicity in wild-type KRAS, cetuximab-treated colorectal cancer patients. FCGR3A genotype may modulate the relationship between FCGR2A polymorphism and outcome. FCGR2A is a promising biomarker for clinical management for these patients.

A Case-Control Study on Association of Ulcerative Colitis with FCGR2A Gene Polymorphisms in Chinese Patients.

BACKGROUND AND AIMS: The Fc gamma receptor IIa (FcγRIIa), encoded by FCGR2A gene, has been suggested to play a crucial role in immunity by linking immunoglobulin G antibody-mediated responses with cellular effector and regulatory functions. Polymorphisms in FCGR2A have been shown to affect FcγRIIa/antibody interactions and have been potentially implicated in several autoimmune and inflammatory conditions. This study was designed to analyze the association between ulcerative colitis (UC) and FCGR2A polymorphisms in the Chinese population. MATERIALS AND METHODS: A total of 422 patients with UC and 710 unaffected controls were recruited. Five single nucleotide polymorphisms of FCGR2A (rs1801274, rs10800309, rs4657039, rs511278, and rs6696854) were genotyped by SNaPshot. Analyses for linkage disequilibrium (LD) and haplotype studies of FCGR2A were performed for all study subjects. RESULTS: The frequency of the minor homozygote (CC) of the rs1801274 SNP of FCGR2A was shown to be significantly lower in patients with UC than in controls (7.1% vs. 12.1%, p = 0.008). Two haplotype blocks, formed by FCGR2A (rs4657039, rs6696854, and rs10800309) and FCGR2A (rs1801274 and rs511278), respectively, were observed in the subsequent LD analysis. The TC haplotype constructed by the major allele of FCGR2A (rs1801274 and rs511278) was more prevalent in UC patients compared with controls (65.2% vs. 60.2%, p = 0.017). CONCLUSIONS: The minor homozygote (CC) of FCGR2A (rs1801274) may contribute to decrease the susceptibility to UC and the TC haplotype formed by FCGR2A (rs1801274 and rs511278) may increase the risk of UC in the Chinese population.

Caracterización de una muestra de pacientes chilenos con periodontitis y frecuencia del polimorfismo H131R en el receptor FcγRIIa / Characterization of a sample Chilean patients with periodontitis and frequency of H131R polymorphism in the FcγRIIa receptor

RESUMEN: Los receptores Fcγ947; (FcγR), específicos para la inmunoglobulina G, les confieren a las células donde se expresan funciones en la respuesta inmunoinflamatoria. La heterogeneidad interindividual en la eficiencia de la función de los FcγR se ha explicado por polimorfismos en los genes que codifican 3 de estos receptores, FcγRIIa, FcγRIIIa y FcγRIIIb, los cuales han sido asociados con susceptibilidad y/o severidad en enfermedades infecciosas y autoinmunes en diferentes poblaciones. En este trabajo se analizan las características clínicas de 94 pacientes chilenos con evidencia de daño periodontal y se establece la frecuencia alélica/genotípica del polimorfismo H131R en el gen FCGR2A que codifica para el receptor FcγRIIa, así como su posible asociación con periodontitis. El polimorfismo G>A (H131R) en el gen FCGR2A se estudió por PCR en tiempo real utilizando sondas TaqMan. En el grupo estudiado se encontró un alto porcentaje de pacientes con periodontitis (86, 2%) y una asociación significativa a edad y sexo. No se observó una asociación a los alelos H o R, ni a los genotipos encontrados (H/R y R/R). Este es el primer trabajo en que se estudia el polimorfismo H131R en el FcγRIIa en población chilena en una muestra de pacientes adecuadamente caracterizados; sin embargo, creemos que es necesario estudiar un mayor número de sujetos para determinar si los polimorfismos de los genes FcγR constituyen o no posibles factores de susceptibilidad a enfermedad periodontal en población chilena.

ABSTRACT: The Fcγ receptors (FcγR) specific for the immunoglobulin G, expresses for the immune inflammatory response function. The inter individual heterogeneity in the efficiency of the FcγR function has been explained by polymorphisms in genes that encode for 3 of these receptors, FcγRIIa, FcγRIIIa and FcγRIIIb, which have been associated with susceptibility or severity in autoimmune and infectious diseases in different populations. This paper discusses the clinical characteristics of 94 Chilean patients with evidence of periodontal damage and establishes the allelic/genotypic frequency of polymorphism H131R in the FCGR2A gene, which encodes for the receptor FcγRIIa, as well as their possible association with periodontitis. Polymorphism G>A (H131R) in the gene FCGR2A was studied via real time PCR using TaqMan probes. In the study group, a high percentage of patients with periodontitis was found (86, 2%) with a significant association with age and gender. No determination could be reached as to whether the allele H or R or the genotypes found (H/R and R/R) were a factor of genetic susceptibility. This is the first study to determine the polymorphisms of the FcγR gene in a Chilean population adequately characterized; nevertheless, we believe that it is necessary to study a greater number of subjects in order to determine if the polymorphisms of the FcγR gene are a possible factors of susceptibility to periodontal disease in the Chilean population.

Pharmacogenetics as Personalized Medicine: Association Investigation of SOD2 rs4880, CYP2C19 rs4244285, and FCGR2A rs1801274 Polymorphisms in a Breast Cancer Population in Iraqi Women.

BACKGROUND: Breast cancer is the most common cancer in women characterized by a high variable clinical outcome among individuals treated with targeted therapies. PATIENTS AND METHODS: In this study, we performed a population-based approach intersecting high-throughput genotype data from Iraqi populations with publicly available pharmacogenomics information to estimate the frequency of genotypes correlated with responsiveness to breast cancer treatment thus improving the clinical management of this disease in an efficient and cost effective way. A total of 50 patients and 25 healthy controls were enrolled in our study. Genotyping of rs4880, rs4244285, and rs1801274 were examined in association with breast cancer in Iraqi women. RESULTS: We found that individuals carrying the CT genotype of rs4880 manifested an increased risk of breast cancer compared with those carrying the TT genotype (odds ratio [OR], 0.171; 95% confidence interval [CI], 0.053-0.551; P = .002). In the dominant model, we observed that the CT and CC genotype of rs4880 showed an increased risk of breast cancer compared with the TT genotype (OR, 0.248; 95% CI, 0.089-0.690; P = .006). Moreover, subjects with the GA genotype of rs4244285 presented a higher risk of breast cancer than the GG genotype (OR, 0.256; 95% CI, 0.066-0.987; P = .038) and dominant models (OR, 0.025; 95% CI, 0.054-0.775; P = .013). CONCLUSION: The analysis revealed that rs1801274 showed linkage disequilibrium and decreased risk of breast cancer. In conclusion, our study suggests that rs4880 and rs4244285 polymorphisms play an important role in development of breast cancer in an Iraqi population, and no significant association was found between rs1801274 and the risk of breast cancer.

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.