CD209-336A/G promotor polymorphism and its clinical associations in sickle cell disease Egyptian Pediatric patients

Afifi, Rasha Abdel-Raouf; Kamal, Dina; Sayed, Riham El; Ekladious, Sherif; Shaheen, Gehan H.; Yousry, Sherif M.; Hussein, Rania Elsayed

doi:10.1016/j.hemonc.2017.09.002

Cited by 6 publications

(3 citation statements)

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“…CD209 encodes dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN), and has been shown to bind various ligands including T-lymphocytes, thus contributing to activation of signal transduction pathways and recognition of infectious agents. Several studies have shown its polymorphic variants to be associated with tolerance or susceptibility to diseases, such as tuberculosis, schistosomiasis, leishmaniasis, and sickle-cell disease [23,27,30,[51][52][53], asserting that the G allele significantly increased the risk of disease. Our results confirm this observation, indicating that mutation of the CD209 gene has a considerable impact on malaria pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…The CD209 protein has been shown to recognize pathogens through its N-terminal domain, binding to ligands on microbes in the process [25], as well as activating the signal transduction pathway in the process. Since DC's are an essential component for antigen presentation, and for initiation of the process mediating adaptive immune responses, its polymorphisms, especially the rs4804803 (snp -336G/A) gene promoter polymorphism, have been shown to modulate disease susceptibility or severity [26][27][28][29][30][31][32]. We have shown previously that this polymorphism tracks ethnicity, with significant genotypic and allelic diversity between African and American sickle-cell disease patients [27].…”

Section: Introductionmentioning

confidence: 98%

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CD209 and Not CD28 or STAT6 Polymorphism Mediates Clinical Malaria and Parasitemia among Children from Nigeria

et al. 2020

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Malaria remains a significant disease, causing epic health problems and challenges all over the world, especially in sub-Saharan Africa. CD209 and CD28 genes act as co-stimulators and regulators of the immune system, while the STAT6 gene has been reported to mediate cytokine-induced responses. Single nucleotide polymorphisms of these genes might lead to differential disease susceptibility among populations at risk for malaria, due to alterations in the immune response. We aim to identify key drivers of the immune response to malaria infection among the three SNPs: CD209 (rs4804803), CD28 (rs35593994) and STAT6 (rs3024974). After approval and informed consent, we genotyped blood samples from a total of 531 children recruited from Nigeria using the Taqman SNP genotyping assay and performed comparative analysis of clinical covariates among malaria-infected children. Our results reveal the CD209 (rs4804803) polymorphism as a susceptibility factor for malaria infection, significantly increasing the risk of disease among children, but not CD28 (rs35593994) or STAT6 (rs3024974) polymorphisms. Specifically, individuals with the homozygous mutant allele (rs4804803G/G) for the CD209 gene have a significantly greater susceptibility to malaria, and presented with higher mean parasitemia. This observation may be due to a defective antigen presentation and priming, leading to an ineffective downstream adaptive immune response needed to combat infection, as well as the resultant higher parasitemia and disease manifestation. We conclude that the CD209 gene is a critical driver of the immune response during malaria infection, and can serve as a predictor of disease susceptibility or a biomarker for disease diagnosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

CD209 and Not CD28 or STAT6 Polymorphism Mediates Clinical Malaria and Parasitemia among Children from Nigeria

et al. 2020

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“…In SCD the spleen is damaged by the sickled blood cells and it is not able to remove bacteria from the blood thus making the patient susceptible for infections apart from the splenic dysfunction, CD209-336 A>G polymorphism also leads to a number of bacterial infections. Genotypic frequency of CD209-336 A>G polymorphism also varies among different ethnic population of SCD patients and CD209-336 A>G polymorphism and bacteria responsible for infection can be used as a predicator of susceptibility to infections in patients with SCD [25].…”

Section: Bacterial Infectionmentioning

confidence: 99%

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2019

RJLBPCS

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Sickle cell disease (SCD) is an autosomal recessive hematological disorder, caused by a single mutation in the beta hemoglobin gene. In SCD the blood cells become crescent or sickle shaped and block the blood capillaries. The blockage of capillaries leads to two main pathophysiologic conditions; hemolysis and vaso-occlusion crisis leading to several acute and chronic clinical complications like pulmonary hypertension, retinopathy, inflammation, oxidative stress etc. These complications alter biological molecules like monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), endothelial nos-3 (eNOS3), toll like receptor (TLR), etc. which destabilize vital organs of our body resulting in organ damage and early mortality in SCD patients. These molecules also serve as a potential biomarker for the identification of level of manifestation of disease. In this review we have focused on some major complications associated with SCD and understanding of these biomarkers and their levels can also help in better assessment and management of complications associated with SCD.

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Genetic Variation and Sickle Cell Disease Severity

Kirkham,

Estepp,

Weiss

et al. 2023

JAMA Netw Open

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ImportanceSickle cell disease (SCD) is a monogenic disorder, yet clinical outcomes are influenced by additional genetic factors. Despite decades of research, the genetics of SCD remain poorly understood.ObjectiveTo assess all reported genetic modifiers of SCD, evaluate the design of associated studies, and provide guidelines for future analyses according to modern genetic study recommendations.Data SourcesPubMed, Web of Science, and Scopus were searched through May 16, 2023, identifying 5290 publications.Study SelectionAt least 2 reviewers identified 571 original, peer-reviewed English-language publications reporting genetic modifiers of human SCD phenotypes, wherein the outcome was not treatment response, and the comparison was not between SCD subtypes or including healthy controls.Data Extraction and SynthesisData relevant to all genetic modifiers of SCD were extracted, evaluated, and presented following STREGA and PRISMA guidelines. Weighted z score meta-analyses and pathway analyses were conducted.Main Outcomes and MeasuresOutcomes were aggregated into 25 categories, grouped as acute complications, chronic conditions, hematologic parameters or biomarkers, and general or mixed measures of SCD severity.ResultsThe 571 included studies reported on 29 670 unique individuals (50% ≤ 18 years of age) from 43 countries. Of the 17 757 extracted results (4890 significant) in 1552 genes, 3675 results met the study criteria for meta-analysis: reported phenotype and genotype, association size and direction, variability measure, sample size, and statistical test. Only 173 results for 62 associations could be cross-study combined. The remaining associations could not be aggregated because they were only reported once or methods (eg, study design, reporting practice) and genotype or phenotype definitions were insufficiently harmonized. Gene variants regulating fetal hemoglobin and α-thalassemia (important markers for SCD severity) were frequently identified: 19 single-nucleotide variants in BCL11A, HBS1L-MYB, and HBG2 were significantly associated with fetal hemoglobin (absolute value of Z = 4.00 to 20.66; P = 8.63 × 10−95 to 6.19 × 10−5), and α-thalassemia deletions were significantly associated with increased hemoglobin level and reduced risk of albuminuria, abnormal transcranial Doppler velocity, and stroke (absolute value of Z = 3.43 to 5.16; P = 2.42 × 10−7 to 6.00 × 10−4). However, other associations remain unconfirmed. Pathway analyses of significant genes highlighted the importance of cellular adhesion, inflammation, oxidative and toxic stress, and blood vessel regulation in SCD (23 of the top 25 Gene Ontology pathways involve these processes) and suggested future research areas.Conclusions and RelevanceThe findings of this comprehensive systematic review and meta-analysis of all published genetic modifiers of SCD indicated that implementation of standardized phenotypes, statistical methods, and reporting practices should accelerate discovery and validation of genetic modifiers and development of clinically actionable genetic profiles.

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CD209-336A/G promotor polymorphism and its clinical associations in sickle cell disease Egyptian Pediatric patients

Abstract: We found no significant difference between our population of Egyptian SCD cases and controls regarding CD209 A>G polymorphism. Infections occurred more frequently among the heterozygous genotype (AG) and homozygous genotype (GG) patients.

Cited by 6 publications

References 30 publications

CD209 and Not CD28 or STAT6 Polymorphism Mediates Clinical Malaria and Parasitemia among Children from Nigeria

CD209 and Not CD28 or STAT6 Polymorphism Mediates Clinical Malaria and Parasitemia among Children from Nigeria

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Genetic Variation and Sickle Cell Disease Severity

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