- Autores: Amorim A, Arez AP, Do Rosário VE, Fernandes N, Gusmão L, Machado P, Manco L, Miranda J, Pereira R, Ribeiro L, Rocha AM
- Ano de Publicação: 2010
- Journal: British journal of haematology
- Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=Malaria%3A+looking+for+selection+signatures+in+the+human+PKLR+gene+region
The genetic component of susceptibility to malaria is both complex and multigenic and the better-known protective polymorphisms are those involving erythrocyte-specific structural proteins and enzymes. In vivo and in vitro data have suggested that pyruvate kinase deficiency, which causes a nonspherocytic haemolytic anaemia, could be protective against malaria severity in humans, but this hypothesis remains to be tested. In the present study, we conducted a combined analysis of Short Tandem Repeats (STRs) and Single Nucleotide Polymorphisms (SNPs) in the pyruvate kinase-encoding gene (PKLR) and adjacent regions (chromosome 1q21) to look for malaria selective signatures in two sub-Saharan African populations from Angola and Mozambique, in several groups with different malaria infection outcome. A European population from Portugal, including a control and a pyruvate kinase-deficient group, was used for comparison. Data from STR and SNP loci spread along the PKLR gene region showed a considerably higher differentiation between African and Portuguese populations than that usually found for neutral markers. In addition, a wider region showing strong linkage disequilibrium was found in an uncomplicated malaria group, and a haplotype was found to be associated with this clinical group. Altogether, this data suggests that malaria selective pressure is acting in this genomic region.