2024-03-28T21:33:45Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/66052023-10-09T12:49:26Zcom_20.500.12105_2074com_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_2075
00925njm 22002777a 4500
dc
Machado, Patrícia
author
Manco, Licínio
author
Gomes, Cláudia
author
Mendes, Cristina
author
Fernandes, Natércia
author
Salomé, Graça
author
Sitoe, Luis
author
Chibute, Sérgio
author
Langa, José
author
Ribeiro, Letícia
author
Miranda, Juliana
author
Ochando, Jordi
author
Pinto, João
author
Amorim, António
author
do Rosário, Virgílio E
author
Arez, Ana Paula
author
2012-10-17
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.
PLoS One. 2012;7(10):e47071.
1932-6203
http://hdl.handle.net/20.500.12105/6605
23082140
10.1371/journal.pone.0047071
1932-6203
PloS one
Pyruvate kinase deficiency in sub-Saharan Africa: identification of a highly frequent missense mutation (G829A;Glu277Lys) and association with malaria