Genetic variants of PKLR are associated with acute pain in sickle cell disease.

ABSTRACT: Acute pain, the most prominent complication of sickle cell disease (SCD), results from vaso-occlusion triggered by sickling of deoxygenated red blood cells (RBCs). Concentration of 2,3-diphosphoglycerate (2,3-DPG) in RBCs promotes deoxygenation by preferentially binding to the low-affinity T conformation of HbS. 2,3-DPG is an intermediate substrate in the glycolytic pathway in which pyruvate kinase (gene PKLR, protein PKR) is a rate-limiting enzyme; variants in PKLR may affect PKR activity, 2,3-DPG levels in RBCs, RBC sickling, and acute pain episodes (APEs). We performed a candidate gene association study using 2 cohorts: 242 adult SCD-HbSS patients and 977 children with SCD-HbSS or SCD-HbSβ0 thalassemia. Seven of 47 PKLR variants evaluated in the adult cohort were associated with hospita

SUBMITTER: Wang X 

PROVIDER: S-EPMC9198922 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature