Pyruvate kinase deficiency: optimization of pkrl gene sequencing and genotypic data analysis in relation to malaria risk

Pyruvate kinase (PK) is the glycolytic enzyme responsible for catalyzing the transphosphorylation of phosphoenolpyruvate into adenosine diphosphate in human red blood cells, producing pyruvate and ATP as the final product of the second phase of glycolysis. Pyruvate kinase deficiency (PKD), with autosomal recessive inheritance, is the most common defect associated with hereditary non-spherocytic hemolytic anemia, characterized by anemia and chronic hemolysis resulting from loss-of-function mutations in the pklr gene. It leads to ATP depletion and increased concentration of 2,3-bisphosphoglycerate (2,3-BPG) in erythrocytes, reducing the half-life of these cells. There is evidence that PKD may contribute to resistance to falciparum malaria, but the same applies to vivax malaria is not known. During her 3-week visit to Brazil, Dr. Ana Paula Arez is expected to participate directly in the training of teams from our laboratory in the following activities distributed throughout her stay: 1. Optimization of protocols for the complete sequencing of the promoter region and of the coding region (13 exons) of the pklr gene in Amazonian populations with previously phenotypically determined PKD; 2. Standardization of techniques for analyzing the relationship between polymorphisms in the genomic region that comprises the pklr locus and the risk of malaria in Amazonian populations; 3. Seminar open to all members of the USP Institute of Biomedical Sciences, with wide dissemination throughout the USP campus, on the most recent results of its cellular and molecular studies on the impact of pyruvate kinase deficiency on the development of plasmodia and its epidemiological consequences, as part of the traditional seminar program of the Department of Parasitology at the Institute of Biomedical Sciences at USP (postgraduate discipline BMP 5761, “Seminars of Parasitology II”). 4. Individualized discussion about research projects, open to all members of the Department of Parasitology at the Institute of Biomedical Sciences at USP (teachers, post-doctoral students and postgraduate and scientific initiation students). 5. Symposium on Malaria, open to all members of the USP Institute of Biomedical Sciences, with wide dissemination throughout the USP campus. This is a mixed event (in-person and online) bringing together all associated and main researchers of the thematic project 2022/11963-3 and their students and post-doctoral fellows, lasting three days. 

Project details

Basic Science

Sep 2024 — Oct 2024

Brazil