Pyruvate Kinase Deficiency in Sub-Saharan Africa: Identification of a Highly Frequent Missense Mutation (G829A;Glu277Lys) and Association with Malaria.


Machado, P; Manco, L; Gomes, C; Mendes, C; Fernandes, N; Salomé, G; Sitoe, L; Chibute, S; Langa, J; Ribeiro, L; Miranda, J; Cano, J; Pinto, J; Amorim, A; do Rosário, VE; Arez, AP; (2012) Pyruvate Kinase Deficiency in Sub-Saharan Africa: Identification of a Highly Frequent Missense Mutation (G829A;Glu277Lys) and Association with Malaria. PLoS One, 7 (10). e47071. ISSN 1932-6203 DOI: https://doi.org/10.1371/journal.pone.0047071

[img]
Preview
Text - Published Version
License:

Download (363kB) | Preview

Abstract

BACKGROUND Pyruvate kinase (PK) deficiency, causing hemolytic anemia, has been associated to malaria protection and its prevalence in sub-Saharan Africa is not known so far. This work shows the results of a study undertaken to determine PK deficiency occurrence in some sub-Saharan African countries, as well as finding a prevalent PK variant underlying this deficiency. MATERIALS AND METHODS Blood samples of individuals from four malaria endemic countries (Mozambique, Angola, Equatorial Guinea and Sao Tome and Principe) were analyzed in order to determine PK deficiency occurrence and detect any possible high frequent PK variant mutation. The association between this mutation and malaria was ascertained through association studies involving sample groups from individuals showing different malaria infection and outcome status. RESULTS The percentage of individuals showing a reduced PK activity in Maputo was 4.1% and the missense mutation G829A (Glu277Lys) in the PKLR gene (only identified in three individuals worldwide to date) was identified in a high frequency. Heterozygous carrier frequency was between 6.7% and 2.6%. A significant association was not detected between either PK reduced activity or allele 829A frequency and malaria infection and outcome, although the variant was more frequent among individuals with uncomplicated malaria. CONCLUSIONS This was the first study on the occurrence of PK deficiency in several areas of Africa. A common PKLR mutation G829A (Glu277Lys) was identified. A global geographical co-distribution between malaria and high frequency of PK deficiency seems to occur suggesting that malaria may be a selective force raising the frequency of this 277Lys variant.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Disease Control
PubMed ID: 23082140
Web of Science ID: 311146900035
URI: http://researchonline.lshtm.ac.uk/id/eprint/375633

Statistics


Download activity - last 12 months
Downloads since deposit
430Downloads
286Hits
Accesses by country - last 12 months
Accesses by referrer - last 12 months
Impact and interest
Additional statistics for this record are available via IRStats2

Actions (login required)

Edit Item Edit Item