Cargando…

Glucose-6-phosphate dehydrogenase polymorphisms and susceptibility to mild malaria in Dogon and Fulani, Mali

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with protection from severe malaria, and potentially uncomplicated malaria phenotypes. It has been documented that G6PD deficiency in sub-Saharan Africa is due to the 202A/376G G6PD A-allele, and association studies have u...

Descripción completa

Detalles Bibliográficos
Autores principales: Maiga, Bakary, Dolo, Amagana, Campino, Susana, Sepulveda, Nuno, Corran, Patrick, Rockett, Kirk A, Troye-Blomberg, Marita, Doumbo, Ogobara K, Clark, Taane G
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110528/
https://www.ncbi.nlm.nih.gov/pubmed/25015414
http://dx.doi.org/10.1186/1475-2875-13-270
_version_ 1782328011598594048
author Maiga, Bakary
Dolo, Amagana
Campino, Susana
Sepulveda, Nuno
Corran, Patrick
Rockett, Kirk A
Troye-Blomberg, Marita
Doumbo, Ogobara K
Clark, Taane G
author_facet Maiga, Bakary
Dolo, Amagana
Campino, Susana
Sepulveda, Nuno
Corran, Patrick
Rockett, Kirk A
Troye-Blomberg, Marita
Doumbo, Ogobara K
Clark, Taane G
author_sort Maiga, Bakary
collection PubMed
description BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with protection from severe malaria, and potentially uncomplicated malaria phenotypes. It has been documented that G6PD deficiency in sub-Saharan Africa is due to the 202A/376G G6PD A-allele, and association studies have used genotyping as a convenient technique for epidemiological studies. However, recent studies have shown discrepancies in G6PD202/376 associations with severe malaria. There is evidence to suggest that other G6PD deficiency alleles may be common in some regions of West Africa, and that allelic heterogeneity could explain these discrepancies. METHODS: A cross-sectional epidemiological study of malaria susceptibility was conducted during 2006 and 2007 in the Sahel meso-endemic malaria zone of Mali. The study included Dogon (n = 375) and Fulani (n = 337) sympatric ethnic groups, where the latter group is characterized by lower susceptibility to Plasmodium falciparum malaria. Fifty-three G6PD polymorphisms, including 202/376, were genotyped across the 712 samples. Evidence of association of these G6PD polymorphisms and mild malaria was assessed in both ethnic groups using genotypic and haplotypic statistical tests. RESULTS: It was confirmed that the Fulani are less susceptible to malaria, and the 202A mutation is rare in this group (< 1% versus Dogon 7.9%). The Betica-Selma 968C/376G (~11% enzymatic activity) was more common in Fulani (6.1% vs Dogon 0.0%). There are differences in haplotype frequencies between Dogon and Fulani, and association analysis did not reveal strong evidence of protective G6PD genetic effects against uncomplicated malaria in both ethnic groups and gender. However, there was some evidence of increased risk of mild malaria in Dogon with the 202A mutation, attaining borderline statistical significance in females. The rs915942 polymorphism was found to be associated with asymptomatic malaria in Dogon females, and the rs61042368 polymorphism was associated with clinical malaria in Fulani males. CONCLUSIONS: The results highlight the need to consider markers in addition to G6PD202 in studies of deficiency. Further, large genetic epidemiological studies of multi-ethnic groups in West Africa across a spectrum of malaria severity phenotypes are required to establish who receives protection from G6PD deficiency.
format Online
Article
Text
id pubmed-4110528
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-41105282014-07-26 Glucose-6-phosphate dehydrogenase polymorphisms and susceptibility to mild malaria in Dogon and Fulani, Mali Maiga, Bakary Dolo, Amagana Campino, Susana Sepulveda, Nuno Corran, Patrick Rockett, Kirk A Troye-Blomberg, Marita Doumbo, Ogobara K Clark, Taane G Malar J Research BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with protection from severe malaria, and potentially uncomplicated malaria phenotypes. It has been documented that G6PD deficiency in sub-Saharan Africa is due to the 202A/376G G6PD A-allele, and association studies have used genotyping as a convenient technique for epidemiological studies. However, recent studies have shown discrepancies in G6PD202/376 associations with severe malaria. There is evidence to suggest that other G6PD deficiency alleles may be common in some regions of West Africa, and that allelic heterogeneity could explain these discrepancies. METHODS: A cross-sectional epidemiological study of malaria susceptibility was conducted during 2006 and 2007 in the Sahel meso-endemic malaria zone of Mali. The study included Dogon (n = 375) and Fulani (n = 337) sympatric ethnic groups, where the latter group is characterized by lower susceptibility to Plasmodium falciparum malaria. Fifty-three G6PD polymorphisms, including 202/376, were genotyped across the 712 samples. Evidence of association of these G6PD polymorphisms and mild malaria was assessed in both ethnic groups using genotypic and haplotypic statistical tests. RESULTS: It was confirmed that the Fulani are less susceptible to malaria, and the 202A mutation is rare in this group (< 1% versus Dogon 7.9%). The Betica-Selma 968C/376G (~11% enzymatic activity) was more common in Fulani (6.1% vs Dogon 0.0%). There are differences in haplotype frequencies between Dogon and Fulani, and association analysis did not reveal strong evidence of protective G6PD genetic effects against uncomplicated malaria in both ethnic groups and gender. However, there was some evidence of increased risk of mild malaria in Dogon with the 202A mutation, attaining borderline statistical significance in females. The rs915942 polymorphism was found to be associated with asymptomatic malaria in Dogon females, and the rs61042368 polymorphism was associated with clinical malaria in Fulani males. CONCLUSIONS: The results highlight the need to consider markers in addition to G6PD202 in studies of deficiency. Further, large genetic epidemiological studies of multi-ethnic groups in West Africa across a spectrum of malaria severity phenotypes are required to establish who receives protection from G6PD deficiency. BioMed Central 2014-07-11 /pmc/articles/PMC4110528/ /pubmed/25015414 http://dx.doi.org/10.1186/1475-2875-13-270 Text en Copyright © 2014 Maiga et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Maiga, Bakary
Dolo, Amagana
Campino, Susana
Sepulveda, Nuno
Corran, Patrick
Rockett, Kirk A
Troye-Blomberg, Marita
Doumbo, Ogobara K
Clark, Taane G
Glucose-6-phosphate dehydrogenase polymorphisms and susceptibility to mild malaria in Dogon and Fulani, Mali
title Glucose-6-phosphate dehydrogenase polymorphisms and susceptibility to mild malaria in Dogon and Fulani, Mali
title_full Glucose-6-phosphate dehydrogenase polymorphisms and susceptibility to mild malaria in Dogon and Fulani, Mali
title_fullStr Glucose-6-phosphate dehydrogenase polymorphisms and susceptibility to mild malaria in Dogon and Fulani, Mali
title_full_unstemmed Glucose-6-phosphate dehydrogenase polymorphisms and susceptibility to mild malaria in Dogon and Fulani, Mali
title_short Glucose-6-phosphate dehydrogenase polymorphisms and susceptibility to mild malaria in Dogon and Fulani, Mali
title_sort glucose-6-phosphate dehydrogenase polymorphisms and susceptibility to mild malaria in dogon and fulani, mali
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110528/
https://www.ncbi.nlm.nih.gov/pubmed/25015414
http://dx.doi.org/10.1186/1475-2875-13-270
work_keys_str_mv AT maigabakary glucose6phosphatedehydrogenasepolymorphismsandsusceptibilitytomildmalariaindogonandfulanimali
AT doloamagana glucose6phosphatedehydrogenasepolymorphismsandsusceptibilitytomildmalariaindogonandfulanimali
AT campinosusana glucose6phosphatedehydrogenasepolymorphismsandsusceptibilitytomildmalariaindogonandfulanimali
AT sepulvedanuno glucose6phosphatedehydrogenasepolymorphismsandsusceptibilitytomildmalariaindogonandfulanimali
AT corranpatrick glucose6phosphatedehydrogenasepolymorphismsandsusceptibilitytomildmalariaindogonandfulanimali
AT rockettkirka glucose6phosphatedehydrogenasepolymorphismsandsusceptibilitytomildmalariaindogonandfulanimali
AT troyeblombergmarita glucose6phosphatedehydrogenasepolymorphismsandsusceptibilitytomildmalariaindogonandfulanimali
AT doumboogobarak glucose6phosphatedehydrogenasepolymorphismsandsusceptibilitytomildmalariaindogonandfulanimali
AT clarktaaneg glucose6phosphatedehydrogenasepolymorphismsandsusceptibilitytomildmalariaindogonandfulanimali