Trusted Resources: Evidence & Education
Scientific literature and patient education texts
Genetic Modifiers Influencing the Development of Albuminuria in Children with Sickle Cell Anemia
source: American Society of Hematology
year: 2015
authors: Beverly A Schaefer, Jonathan M Flanagan, Banu Aygun, Ofelia A. Alvarez, Stephen C Nelson, Kerri A Nottage, Carla W Roberts, Thad A. Howard, Barry R Davis, Russell E. Ware
summary/abstract:Background: Nephropathy in sickle cell anemia (SCA) begins in childhood and portends chronic kidney disease, renal failure, and early mortality among affected adults. Individuals of African descent have disproportionately higher rates of developing non-diabetic renal disease. Several candidate genetic variants have been identified, including some specific to African Americans, which are associated with the development of albuminuria and renal disease. The influence of genetic polymorphisms on albuminuria and elevated glomerular filtration rate (GFR) in children with SCA, both early signs of sickle nephropathy, has not been investigated.
Objectives: To determine the influence of selected single nucleotide polymorphisms (SNPs) on the development of albuminuria and elevated GFR in children with SCA; to identify novel genetic variants influencing albuminuria and GFR by whole exome sequencing (WES).
Design/Methods: Genomic DNA was collected on children with SCA enrolled in two prospective studies with pre-hydroxyurea renal assessments (n=185): (1) Hydroxyurea Study of Long-Term Effects (HUSTLE, NCT00305175, n=79) with no prior disease-modifying therapy; and (2) Transcranial Doppler (TCD) With Transfusions Changing to Hydroxyurea (TWiTCH, NCT 01425307, n=106) on chronic transfusions for abnormal TCD velocities. Albuminuria was defined as ≥30mg albumin/gm creatinine on the pre-hydroxyurea urine specimen. GFR was measured in HUSTLE using plasma DTPA (technetium 99m-labeled diethylenetriaminepentaacetic acid) clearance, and estimated GFR (eGFR) in TWiTCH based on serum creatinine. DNA samples were genotyped for 8 candidate SNPs previously associated with renal disease, using PCR-based allelic discrimination, bidirectional Sanger sequencing, and analysis of variable number tandem repeats (VNTR). Associations between albuminuria and genetic polymorphisms were tested using an additive model and correlation trend test. Linked WES data from the same patients were analyzed to identify other variants associated with albuminuria and GFR.
organization: Cincinnati Children's Hospital Medical Center; Baylor College of Medicine, Houston; Cohen Children's Medical Center of New York; Univ. of Miami School of Med.; Children's Hospitals and Clinics of Minnesota; St. Jude Children's Research Hospital, Memphis; University of South Carolina; University of Texas School of Public Healthread more
Related Content
-
Acute kidney injury in children with sickle cell disease-compounding a chronic problemIn an article recently published in Pedi...
-
Prevalence and Correlates of Growth Failure in Young African Patients With Sickle Cell DiseaseGrowth failure (GF) in children with sic...
-
FDA Awards $2M to Phase 2 Trial of Vitamin D for Reducing Risk of SCD Respiratory ComplicationsThe U.S. Food and Drug Administration (F...
-
Hydroxyurea Treatment in Men with SCA Leads to Drop in Total Sperm Count, Study ShowsResearchers found that treatment with hy...
-
How This Disease Changes the Shape of Your Cells – Amber M. Yateshttps://www.youtube.com/watch?v=hRnrIpUM...
-
More Online Queries in Winter Suggest Seasonal Variations in SCD ActivityMore people search for information on si...
-
Today’s Faces of Sickle Cell Disease: Tesha SamuelsTesha Samuels was diagnosed with SCD at ...
To improve your experience on this site, we use cookies. This includes cookies essential for the basic functioning of our website, cookies for analytics purposes, and cookies enabling us to personalize site content. By clicking on 'Accept' or any content on this site, you agree that cookies can be placed. You may adjust your browser's cookie settings to suit your preferences. More Information
The cookie settings on this website are set to "allow cookies" to give you the best browsing experience possible. If you continue to use this website without changing your cookie settings or you click "Accept" below then you are consenting to this.