ArticlePloS one2016
Genetic Modifiers of White Blood Cell Count, Albuminuria and Glomerular Filtration Rate in Children with Sickle Cell Anemia.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 4 syntheses or guidelines pooled it, 36 citations in OpenAlex.
- Clinical and Genetic Predictors of Sickle Cell Nephropathy: A Global Systematic Review.Omics : a journal of integrative biology · 2025Pooled it
- Systematic Review of Genetic Modifiers Associated with the Development and/or Progression of Nephropathy in Patients with Sickle Cell Disease.International journal of molecular sciences · 2024Pooled it
- Genetic Variation and Sickle Cell Disease Severity: A Systematic Review and Meta-Analysis.JAMA network open · 2023Pooled it
- Genome-wide meta-analysis identifies new candidate genes for sickle cell disease nephropathy.Blood advances · 2023Pooled it
- Urinary megalin expression in children with sickle cell nephropathy.Pediatric nephrology (Berlin, Germany) · 2026Article
- Natural History of Chronic Kidney Disease in Sickle Cell Disease.American journal of hematology · 2026Review
- Management of Kidney Disease with Sickle Cell Disease.Journal of the American Society of Nephrology : JASN · 2025Review
- The modern use of hydroxyurea for children with sickle cell anemia.Haematologica · 2025Review
- Natural history and variability in albuminuria in pediatric and murine sickle cell anemia.Blood advances · 2023Article
- Variation and impact of polygenic hematologic traits in monogenic sickle cell disease.Haematologica · 2023Article
- The nephropathy of sickle cell trait and sickle cell disease.Nature reviews. Nephrology · 2022Review
- Investigations of Kidney Dysfunction-Related Gene Variants in Sickle Cell Disease Patients in Cameroon (Sub-Saharan Africa).Frontiers in genetics · 2021Article
- Impaired Bile Secretion Promotes Hepatobiliary Injury in Sickle Cell Disease.Hepatology (Baltimore, Md.) · 2020Article
- Combining clinical and candidate gene data into a risk score for azathioprine-associated leukopenia in routine clinical practice.The pharmacogenomics journal · 2020Article
- Assessment of Hemoglobin Variants in Patients Receiving Health Care at the Ho Teaching Hospital: A Three-Year Retrospective Study.Advances in hematology · 2020Article
- Genetic Modifiers at the Crossroads of Personalised Medicine for Haemoglobinopathies.Journal of clinical medicine · 2019Article
- APOL1 and kidney cell function.American journal of physiology. Renal physiology · 2019Review
- Hyperfiltration during early childhood precedes albuminuria in pediatric sickle cell nephropathy.American journal of hematology · 2019Article
- Clinical and metabolomic risk factors associated with rapid renal function decline in sickle cell disease.American journal of hematology · 2018Article
- Genetic ancestry and population differences in levels of inflammatory cytokines in women: Role for evolutionary selection and environmental factors.PLoS genetics · 2018Observational
Corrections and comments
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Authors and funding
12 authors at 9 institutions in 1 country.
Funding
Abstract
Discovery and validation of genetic variants that influence disease severity in children with sickle cell anemia (SCA) could lead to early identification of high-risk patients, better screening strategies, and intervention with targeted and preventive therapy. We hypothesized that newly identified genetic risk factors for the general African American population could also impact laboratory biomarkers known to contribute to the clinical disease expression of SCA, including variants influencing the white blood cell count and the development of albuminuria and abnormal glomerular filtration rate. We first investigated candidate genetic polymorphisms in well-characterized SCA pediatric cohorts from three prospective NHLBI-supported clinical trials: HUSTLE, SWiTCH, and TWiTCH. We also performed whole exome sequencing to identify novel genetic variants, using both a discovery and a validation cohort. Among candidate genes, DARC rs2814778 polymorphism regulating Duffy antigen expression had a clear influence with significantly increased WBC and neutrophil counts, but did not affect the maximum tolerated dose of hydroxyurea therapy. The APOL1 G1 polymorphism, an identified risk factor for non-diabetic renal disease, was associated with albuminuria. Whole exome sequencing discovered several novel variants that maintained significance in the validation cohorts, including ZFHX4 polymorphisms affecting both the leukocyte and neutrophil counts, as well as AGGF1, CYP4B1, CUBN, TOR2A, PKD1L2, and CD163 variants affecting the glomerular filtration rate. The identification of robust, reliable, and reproducible genetic markers for disease severity in SCA remains elusive, but new genetic variants provide avenues for further validation and investigation.
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