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.
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Between 18 and 80 years of age
African or of African descent
Capacity to consent is required
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.
The study will be listed on the clinicaltrials.gov, Clinical Center research studies, and the National Heart, Lung and Blood Institute patient recruitment websites. Patients who are followed on other NHLBI sickle cell protocols may be asked to participate in this study, particularly subjects enrolled in the Natural History of Sickle Cell Disease (NCT00081523; 04-H-0161).
Case-control
Cross-sectional
Not listed
Genotype the 4 PKLR intron-2 variants
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
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
Assess correlation between the quantitative assays and genotype
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