Lack of association between the Duffy antigen receptor for chemokines (DARC) expression and clinical outcome of children with sickle cell anemia

Araujo, Nara B.; Domingos, Igor F.; Medeiros, Fernanda; Hatzlhofer, Betânia Lucena Domingues; Mendonça, Taciana Furtado de; Vasconcelos, Luydson Richardson Silva; Cavalcanti, María Auxiliadora de Queiroz; Araújo, Aderson S; Oliveira, Maria do Carmo Valgueiro Costa de; Lucena-Araújo, Antonio R.; Bezerra, Marcos André Cavalcanti

doi:10.1016/j.imlet.2015.05.015

Cited by 2 publications

(1 citation statement)

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“…The same group (112) reported an effect of these two chemokines on the activation of α4β1 integrin in sickle reticulocytes expressing DARC, resulting in a greater adhesion of sickle RBCs to immobilized VCAM-1 and fibronectin. These findings could partly explain why Drasar et al (113) reported that SCD patients with RBCs expressing DARC could be more prone to developing leg ulcers and kidney disease than Duffy-negative SCD patients, although this association between Duffy phenotype and SCD clinical severity is still debated (114,115). Nebor et al (116) failed to find an association between Duffy phenotype and the clinical severity in a large cohort of SCD patients, but they reported higher plasma IL-8 and RANTES levels in Duffypositive vs. Duffy-negative patients, suggesting that RBCs can clearly modulate the level of inflammation in SCD.…”

Section: Inflammation and Rbcsmentioning

confidence: 99%

The Red Blood Cell—Inflammation Vicious Circle in Sickle Cell Disease

2020

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Section: Inflammation and Rbcsmentioning

confidence: 99%

The Red Blood Cell—Inflammation Vicious Circle in Sickle Cell Disease

2020

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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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Lack of association between the Duffy antigen receptor for chemokines (DARC) expression and clinical outcome of children with sickle cell anemia

Cited by 2 publications

References 8 publications

The Red Blood Cell—Inflammation Vicious Circle in Sickle Cell Disease

The Red Blood Cell—Inflammation Vicious Circle in Sickle Cell Disease

Genetic Variation and Sickle Cell Disease Severity

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