J. BerghoutS. HigginsC. LoucoubarA. SakuntabhaiK. C. KainP. GrosMcGill UniversityUniversity of TorontoInstitut Pasteur, ParisMahidol University2018-06-112018-06-112012-01-01Genes and Immunity. Vol.13, No.1 (2012), 98-10214765470146648792-s2.0-84855933900https://repository.li.mahidol.ac.th/handle/123456789/13868Previously, we have shown that pyruvate kinase, liver and red cell isoform (PKLR) deficiency protects mice in vivo against blood-stage malaria, and observed that reduced PKLR function protects human erythrocytes against Plasmodium falciparum replication ex vivo. Here, we have sequenced the human PKLR gene in 387 individuals from malaria-endemic and other regions in order to assess genetic variability in different geographical regions and ethnic groups. Rich genetic diversity was detected in PKLR, including 59 single-nucleotide polymorphisms and several loss-of-function variants (frequency 1.5%). Haplotype distribution and allele frequency varied considerably with geography. Neutrality testing suggested positive selection of the genein the sub-Saharan African and Pakistan populations. It is possible that such positive selection involves the malarial parasite. © 2012 Macmillan Publishers Limited All rights reserved.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyImmunology and MicrobiologyMedicineArticleSCOPUS10.1038/gene.2011.54