Novel association of FCGR2A polymorphism with age-related macular degeneration (AMD) and development of a novel CFH real-time genotyping method

Velissari, Aliki; Skalidakis, Iosif; Oliveira, Samantha C.; Koutsandrea, Chryssanthi; Kitsos, George; Petersen, Michael B.; Kroupis, Christos

doi:10.1515/cclm-2014-0920

Cited by 7 publications

(9 citation statements)

References 33 publications

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“…The human FCGR2A gene contains at least 800 single-nucleotide polymorphisms (SNPs), located on chromosome 1q23.3 ( Velissari et al, 2015 ). Under physiological conditions, activated FCGriia is constitutively expressed in platelets, neutrophils, macrophages, and dendritic cells, thereby providing an important link between cellular and humoral immunity through a cross-talk between IgG antibody–antigen complexes ( Gillis et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis Identifies Molecular Markers Regulating Development and Progression of Endometriosis and Potential Therapeutic Drugs

Peng

Zheng

et al. 2021

Front. Genet.

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Endometriosis, a common disease that presents as polymorphism, invasiveness, and extensiveness, with clinical manifestations including dysmenorrhea, infertility, and menstrual abnormalities, seriously affects quality of life in women. To date, its underlying etiological mechanism of action and the associated regulatory genes remain unclear. This study aimed to identify molecular markers and elucidate mechanisms underlying the development and progression of endometriosis. Specifically, we downloaded five microarray expression datasets, namely, GSE11691, GSE23339, GSE25628, GSE7305, and GSE105764, from the Gene Expression Omnibus (GEO) database. These datasets, obtained from endometriosis tissues, alongside normal controls, were subjected to in-depth bioinformatics analysis for identification of differentially expressed genes (DEGs), followed by analysis of their function and pathways via gene ontology (GO) and KEGG pathway enrichment analyses. Moreover, we constructed a protein–protein interaction (PPI) network to explore the hub genes and modules, and then applied machine learning algorithms support vector machine-recursive feature elimination and least absolute shrinkage and selection operator (LASSO) analysis to identify key genes. Furthermore, we adopted the CIBERSORTx algorithm to estimate levels of immune cell infiltration while the connective map (CMAP) database was used to identify potential therapeutic drugs in endometriosis. As a result, a total of 423 DEGs, namely, 233 and 190 upregulated and downregulated, were identified. On the other hand, a total of 1,733 PPIs were obtained from the PPI network. The DEGs were mainly enriched in immune-related mechanisms. Furthermore, machine learning and LASSO algorithms identified three key genes, namely, apelin receptor (APLNR), C–C motif chemokine ligand 21 (CCL21), and Fc fragment of IgG receptor IIa (FCGR2A). Furthermore, 16 small molecular compounds associated with endometriosis treatment were identified, and their mechanism of action was also revealed. Taken together, the findings of this study provide new insights into the molecular factors regulating occurrence and progression of endometriosis and its underlying mechanism of action. The identified therapeutic drugs and molecular markers may have clinical significance in early diagnosis of endometriosis.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis Identifies Molecular Markers Regulating Development and Progression of Endometriosis and Potential Therapeutic Drugs

Peng

Zheng

et al. 2021

Front. Genet.

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“…When examining the effect of all significant SNPs determined in this study ( ARMS2 and both SNPs of the TLR4 genes) and all clinical variables with binary logistic regression for the prediction of AMD, it was found that, among the three genes, only ARMS2 shows a strong effect on the development of AMD due to the rarity of TLR4 risk alleles ( Table 6 ). If we also include the results for CFH and FCGR2A SNPs in the same population that were obtained from our previous study, 31 these two SNPs and ARMS2 remain strong in the model of AMD prediction, albeit with reduced ORs ( Table S2 ).…”

Section: Resultsmentioning

confidence: 93%

“…So far, in the Greek population genetic studies exist on ARMS2 , CFH , FCGR2A , C3 , C2 , and BF genes, 31 – 33 but there were no data on TLR4 (Asp299Gly and Thr399Ile) and CD14 (C260T) allele frequencies in Greek patients with AMD. Both genes operate in the same pathway of inflammatory response, and the TLR4 variations Asp299Gly and Thr399Ile affect the extracellular domain of the corresponding protein and result in a differential response to LPS.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, taking into consideration the results from our previous study on AMD that includes the CFH and FCGR2A genes 31 and the clinical and environmental factors, now we have a much broader view of the effect that all genes have on the development of wet AMD ( Table S2 ). The strong genetic component in AMD is clearly demonstrated when only genes remain as strong predictors: in the logistic regression model, the ARMS2 gene shows the strongest association with the disease followed by FCGR2A – an innate immunity gene studied for the first time in AMD from our research team 31 and, finally, the CFH gene, another established factor. Similar study for the aforementioned genes must be replicated for the dry form of AMD as well.…”

Section: Discussionmentioning

confidence: 99%

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Investigation of associations of ARMS2, CD14, and TLR4 gene polymorphisms with wet age-related macular degeneration in a Greek population

Sarli

Skalidakis

Velissari

et al. 2017

OPTH

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BackgroundAge-related macular degeneration (AMD) is a multifactorial degenerative ocular disease that leads to loss of central vision. Functional gene polymorphisms have already been associated with the disease (for example, ARMS2 A69S, rs10490924).AimThe goal of our study was to verify the correlation of the aforementioned ARMS2 variation with the disease, to examine, for the first time, the role of the CD14 C260T variation (rs2569190), and to investigate the association of two TLR4 polymorphisms (Asp299Gly or rs4986790 and Thr399Ile or rs4986791) in a Greek population with the wet form of AMD.Patients and methodsGenomic DNAs were isolated from blood samples of 103 healthy controls and 120 Greek patients with wet AMD who were age- and sex-matched, and all of whom were clinically evaluated. For the genotyping of all selected polymorphisms, polymerase chain reaction–restriction fragment length polymorphism analysis was performed.Results and conclusionsThis study confirmed the association between the ARMS2 variation and AMD, detecting the T risk allele in a significantly higher frequency in the patient group, compared with the control subjects (45% vs 29.13%, P<0.001, odds ratio [OR] 1.99, confidence interval 1.34–2.95). For the CD14 polymorphism, no statistically significant correlation was observed. As for the TLR4 polymorphisms, the percentage of heterozygotes increased from 2.9% to 11.7% in the patient population for Asp299Gly and from 1.9% to 10% for the Thr399Ile polymorphism (ORs 4.40 [P=0.01] and 5.61 [P=0.0088], respectively). Although our ARMS2 and CD14 results provided definite conclusions, the role of innate immunity TLR4 gene awaits further investigation in larger AMD populations with more clinical data collected on past microbial infections.

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“…From various runs of the standard curves, cycle quantification (Cq) of the standards and curve characteristics (slope and intercept) were collected and the coefficient of variation (CV%) for the standards for within-run and between-run precision was estimated. The efficiency (E) of the realtime PCR assay was calculated with the equation E=10 −1/slope as previously described (34). COL8A2 assay.…”

Section: Tcf4 (Rs613872) Novel Real-time Polymerase Chain Reaction (Pcr)mentioning

confidence: 99%

TCF4andCOL8A2Gene Polymorphism Screening in a Greek Population of Late-onset Fuchs Endothelial Corneal Dystrophy

Moschos

Diamantopoulou

Gouliopoulos

et al. 2019

In Vivo

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Background/Aim: Fuchs' endothelial corneal dystrophy (FECD) is a hereditary, progressive, bilateral, and irreversible disorder of the corneal endothelium. The purpose of this study was to develop a novel, accurate and highthroughput real-time polymerase chain reaction (PCR) method and melting-curve analysis in order to genotype the rs613872 polymorphism in the transcription factor 4 (TCF4) gene and to implement it on a well-ascertained sample of 22 Greek FECD patients and 58 healthy individuals, age-and sexmatched. Patients and Methods: DNA was extracted from blood samples, which were screened with the DNA sequencing method in order to detect the g.31753T>G/p.L450W (rs8035192) and g.31767C>A/p.Q455K (rs8035191) mutations in a COL8A2 genomic region. Results: TCF4 risk G allele frequency increased to 48% in FECD patients compared to 17% in healthy-subjects [OR=4.82 (95% CI=1.98-11.73)]. No p.L450W and p.Q455K COL8A2 gene mutations were detected. Conclusion: We confirmed that rs613872 in the TCF4 gene is strongly and statistically associated with late-onset FECD in a Greek population.Fuchs' endothelial corneal dystrophy (FECD) is a hereditary, progressive, bilateral, and irreversible disorder of the corneal 963 This article is freely accessible online.

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Novel association of FCGR2A polymorphism with age-related macular degeneration (AMD) and development of a novel CFH real-time genotyping method

Cited by 7 publications

References 33 publications

Bioinformatics Analysis Identifies Molecular Markers Regulating Development and Progression of Endometriosis and Potential Therapeutic Drugs

Bioinformatics Analysis Identifies Molecular Markers Regulating Development and Progression of Endometriosis and Potential Therapeutic Drugs

Investigation of associations of <em>ARMS2</em>, <em>CD14</em>, and <em>TLR4</em> gene polymorphisms with wet age-related macular degeneration in a Greek population

TCF4andCOL8A2Gene Polymorphism Screening in a Greek Population of Late-onset Fuchs Endothelial Corneal Dystrophy

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