NCT03685721 · National Heart, Lung, and Blood Institute (NHLBI)
Genotype -Phenotype Correlation of PKLR Variants With Pyruvate Kinase, 2,3-Diphosphglycerate and Adenosine Triphosphate Activities in Red Blood Cells of People With Sickle Cell Disease
What this study is about
Background: Some people with the same disorder on a genetic level have more complications than others. Researchers want to look for a link between the PKLR gene and sickle cell disease (SCD) symptoms. The PKLR gene helps create a protein, called pyruvate kinase that is essential in normal functioning of the red blood cell.
View original scientific description
Background: Some people with the same disorder on a genetic level have more complications than others. Researchers want to look for a link between the PKLR gene and sickle cell disease (SCD) symptoms. The PKLR gene helps create a protein, called pyruvate kinase that is essential in normal functioning of the red blood cell. Differences in the PKLR gene, called genetic variants, may cause some changes in the pyruvate kinase protein and other proteins, that can affect functioning of the red blood cell adding to the effect of SCD. Researchers can study these differences by looking at DNA (the material that determines inherited characteristics). Objective: To study how the PKLR gene affects sickle cell disease. Eligibility: Adults ages 18-80 of African descent. They may have sickle cell disease or not. They must not have had a transfusion recently or have a known deficiency of pyruvate kinase. They cannot be pregnant. Design: Participants will be screened with questions. Participants will have blood drawn by needle in an arm vein. The blood will be genetically tested. Not much is known about how genes affect SCD, so the test results will not be shared with participants or their doctors. ...
Primary outcome measures
Genotype the 4 PKLR intron-2 variants
Time frame: Upon enrollment of each subject
To have genotyped the 4 PKLR intron-2 variants in SCD patients from the NHLBI cohort using genomic DNA and compare them to a cohort of healthy ethnic-matched non-SCD controls and a cohort of sickle cell trait carriers, with those reported in 1000 genome project (http://www.1000genomes.org).
Analysis of PK-R transcriptome in red blood cells
Time frame: Interim analysis performed for each group N=125
Have a correlated profile of the PK-R RNA sequence with the 4 PKLR intronic genetic variants.
Correlation of 2,3-DPG, ATP and pyruvate kinase activities with PKLR intron-2 variants
Time frame: Interim analysis performed for each group N=125
Assess correlation between the quantitative assays and genotype
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- INCLUSUION CRITERIA:
- Between 18 and 80 years of age
- African or of African descent
- Capacity to consent is required EXCLUSION CRITERIA:
- Self-reported history of blood transfusion within the last 8 weeks
- Known to have pyruvate kinase deficiency and be on AG348
- All volunteers will undergo the consent process under this protocol to allow for eligibility assessment. Once they have been consented to participate, they will undergo procedures per Protocol.
Exclusion criteria
- Self-reported history of blood transfusion within the last 8 weeks
- Known to have pyruvate kinase deficiency and be on AG348
- All volunteers will undergo the consent process under this protocol to allow for eligibility assessment. Once they have been consented to participate, they will undergo procedures per Protocol.
Where
- Bethesda, Maryland
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Data: ClinicalTrials.gov · synced Jul 15, 2026 · Source of record for eligibility and locations