Interleukin-1β and interleukin-6 gene polymorphisms are associated with manifestations of sickle cell anemia

Vicari, Perla; Adegoke, Samuel Ademola; Mazzotti, Diego R.; Cançado, Rodolfo Delfini; Nogutti, Maria Aparecida Eiko; Figueiredo, Maria Stella

doi:10.1016/j.bcmd.2014.12.004

Cited by 28 publications

(42 citation statements)

References 41 publications

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“…Our study also observed higher frequency of the GG genotype (80.8% in the case group and 77.7% in the control group) and low frequency of the CC genotype (1.1% in the case group and 2.1% in the control group); the frequency of the heterozygous genotype CG was 18.1% in the case group and 20.2% in the control group. In the Brazilian population, the CC genotype was not present among patients with anemia, and only 3% of the control individuals showed these genotypes (Vicari et al, 2015). These authors also found higher frequency of the GG genotype in the case (78%) and control group (68%).…”

Section: Discussionsupporting

confidence: 57%

“…These frequencies are different from those observed in other ethnic groups, varying of 0.40 in Europeans from the United Kingdom, 0.15 in Gujarati Indian, and 0.05 in the Afro-Caribbean (Fishman et al, 1998). In Brazilians, the study of Vicari et al (2015) showed a C allele frequency of 0.14 in patients with anemia and 0.15 in the control group. Teixeira et al (2014) observed similar frequencies in individuals with periodontitis (0.15) and the control group (0.17).…”

Section: Discussionmentioning

confidence: 67%

“…The frequency of the heterozygous genotype GC was 17.2% in the case group and 27.6% in the control group, while the genotype CC was 6.7% in the case group and 3.1% in the control group. Vicari et al (2015) observed in Brazilians with sickle-cell anemia that the genotype GG was most frequent in the case (74%) and the control (75%) groups. The GC genotype presented frequency of 24 and 20% in both groups, and the genotype CC was present in only 2% of the case individuals and 5% of the control group.…”

Section: Discussionmentioning

confidence: 99%

“…A study in a Chinese population showed that the frequency of the G allele was 99.48%, and the A allele was 0.52% (Gao et al, 2014). The study performed by Vicari et al (2015) in the Brazilian population showed that the frequency of the polymorphic A allele was 15% in anemia patients and 17% in the control group.…”

Section: Discussionmentioning

confidence: 99%

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Research Article Polymorphisms of interleukin 6 in Down syndrome individuals: a case-control study.

Mattos¹,

Uback²,

Biselli-Chicote³

et al. 2017

Genet. Mol. Res.

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Brazil. Genotyping was performed by allelic discrimination technique by real-time polymerase chain reaction using TaqMan SNP Genotyping Assays (Applied Biosystems). There was no difference in the genotype frequency between individuals with and without DS for the evaluated polymorphisms (P > 0.05). The frequency of interleukin 6 polymorphisms did not differ significantly between individuals with and without DS in the casuistic analyzed.

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Research Article Polymorphisms of interleukin 6 in Down syndrome individuals: a case-control study.

Mattos¹,

Uback²,

Biselli-Chicote³

et al. 2017

Genet. Mol. Res.

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“…In a previous evaluation of the pro-inflammatory cytokine IL1β in SCD patients, expression was increased in PBMCs relative to healthy controls, 51 while we found decreased expression in the MSCs of our SCD subjects (notably with the largest CT difference). Similar to other inflammatory diseases, polymorphisms of IL1β have been associated with clinical severity of SCD, 52 presumably related to elevated IL1β. The differential expression of IL1β in our study may be due to either our younger, less clinically affected SCD cohort and/or due to inherent differences in IL1β expression in MSCs versus PBMCs.…”

Section: Discussionmentioning

confidence: 95%

Bone Marrow–Derived Mesenchymal Stromal Cells from Patients with Sickle Cell Disease Display Intact Functionality

Stenger

Chinnadurai

Yuan

et al. 2017

Biology of Blood and Marrow Transplantation

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Summary Hematopoietic cell transplantation (HCT) is the only cure for sickle cell disease (SCD), but engraftment remains challenging in patients lacking matched donors. Infusion of mesenchymal stromal cells (MSCs) at time of HCT may promote hematopoiesis and ameliorate graft-versus-host disease. Experimental murine models suggest MSC major histocompatibility complex compatibility with recipient impacts their in vivo function, suggesting autologous MSCs could be superior to third-party MSCs for promoting HCT engraftment. Here we tested whether bone marrow (BM)-derived MSCs from SCD subjects have comparable functionality compared to MSCs from healthy volunteers. SCD MSC doubling time and surface marker phenotype did not differ significantly from non-SCD. Third-party and autologous (SCD) T cell proliferation was suppressed in a dose-dependent manner by all MSCs. SCD MSCs comparably expressed indoleamine 2,3 dioxygenase, which based upon transwell and blocking experiments, appeared to be the dominant immunomodulatory pathway. The expression of key genes involved in hematopoietic stem cell (HSC)/MSC interactions was minimally altered between SCD and non-SCD MSCs. Expression was, however, altered by IFN-γ stimulation, particularly CXCL14, CXCL26, CX3CL1, CKITL, and JAG1, indicating the potential to augment MSC expression by cytokine stimulation. These data demonstrate the feasibility of expanding BM-derived MSCs from SCD patients that phenotypically and functionally do not differ per International Society of Cell Therapy essential criteria from non-SCD MSCs, supporting initial evaluation (primarily for safety) of autologous MSCs to enhance haploidentical HSC engraftment in 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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Interleukin-1β and interleukin-6 gene polymorphisms are associated with manifestations of sickle cell anemia

Cited by 28 publications

References 41 publications

Research Article Polymorphisms of interleukin 6 in Down syndrome individuals: a case-control study.

Research Article Polymorphisms of interleukin 6 in Down syndrome individuals: a case-control study.

Bone Marrow–Derived Mesenchymal Stromal Cells from Patients with Sickle Cell Disease Display Intact Functionality

Genetic Variation and Sickle Cell Disease Severity

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