Do Alpha Thalassemia, Fetal Hemoglobin, and the UGT1A1 Polymorphism have an Influence on Serum Bilirubin Levels and Cholelithiasis in Patients with Sickle Cell Disease?

Azevedo, Laura Alencastro de; Bonazzoni, Joyce Bulcão; Wagner, Sandrine Comparsi; Farias, Mariela Granero; Bittar, Christina; Daudt, Liane Esteves; Castro, Simone Martins de

doi:10.1007/s40291-017-0283-y

Cited by 3 publications

(1 citation statement)

References 25 publications

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“…Initially, the literature search retrieved 1135 published articles. After exclusion of studies because of irrelevance and insufficient data to estimate the outcomes of interest, a total of 34 eligible studies published from 1977 to 2020, which met the eligibility for data extraction and analyses, were used for qualitative and quantitative synthesis; 15 studies from Africa, 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 seven studies from the South America and North America, 42 , 43 , 44 , 45 , 46 , 47 , 48 seven studies from Asia, 8 , 49 , 50 , 51 , 52 , 53 , 54 and four studies from Europe. 55 , 56 , 57 , 58 Overall, this analysis included a total of 6771 SCD patients.…”

Section: Resultsmentioning

confidence: 99%

Correlates of gallbladder stones among patients with sickle cell disease: A meta‐analysis

et al. 2021

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Sickle cell disorders are the most common hemoglobinopathies worldwide. Clinical variability of sickle cell disease (SCD) and susceptibility to its complications have been attributed to hematologic, genetic, and other influencing factors. This review aimed to provide further summary and analyses of the prevalence and factors associated with cholelithiasis among patients with SCD. A systematic database search was conducted in MEDLINE (PubMed), ScienceDirect, Google Scholar, World Health Organization Virtual Health Library, Cochrane Library databases, and System for Information on Gray Literature in Europe (SIGLE). Pooled prevalence, odds ratio (OR), and standardized mean difference (SMD) with the corresponding 95% confidence interval (CI) were calculated using Comprehensive Meta‐Analysis Software version 3.3. A total of 34 studies that fulfilled the eligibility criteria were included in the analyses. The overall prevalence of cholelithiasis among SCD patients was 25.3% (95% CI 19.4–32.3%). The risk of developing cholelithiasis was significantly associated with lower total hemoglobin level (SMD = −0.45; P = 0.002), lower hemoglobin F (HbF) level (SMD = −0.85; P = 0.003), higher total serum bilirubin level (SMD = 1.15; P < 0.001), higher reticulocytes count (SMD = 0.44; P = 0.007), and UDP‐glucuronosyltransferase‐1A1 enzyme (UGT1A1) promoter polymorphism. This review provides a comprehensive view of the high rate of cholelithiasis and its associated factors in SCD patients.

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Section: Resultsmentioning

confidence: 99%

Correlates of gallbladder stones among patients with sickle cell disease: A meta‐analysis

et al. 2021

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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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Influence of UGT1A1 promoter polymorphism, α-thalassemia and βs haplotype in bilirubin levels and cholelithiasis in a large sickle cell anemia cohort

et al. 2021

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Do Alpha Thalassemia, Fetal Hemoglobin, and the UGT1A1 Polymorphism have an Influence on Serum Bilirubin Levels and Cholelithiasis in Patients with Sickle Cell Disease?

Abstract: These preliminary findings suggest that the UGT1A1 gene can influence serum bilirubin levels in sickle cell anemia and serve as a tool to differentiate an acute hemolytic condition from a pre-existing condition of hyperbilirubinemia.

Cited by 3 publications

References 25 publications

Correlates of gallbladder stones among patients with sickle cell disease: A meta‐analysis

Correlates of gallbladder stones among patients with sickle cell disease: A meta‐analysis

Genetic Variation and Sickle Cell Disease Severity

Influence of UGT1A1 promoter polymorphism, α-thalassemia and βs haplotype in bilirubin levels and cholelithiasis in a large sickle cell anemia cohort

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