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

Malaria Journal

Research

Marita Troye-Blomberg¹  Taane G Clark²  Nuno Sepulveda³  Patrick Corran⁴  Ogobara K Doumbo⁵  Amagana Dolo⁵  Bakary Maiga⁶  Kirk A Rockett⁷  Susana Campino⁸ 

[1] Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden;Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, UK;Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, UK;Centre of Statistics and Applications of University of Lisbon, Campo Grande, 1749-016, Lisbon, Portugal;Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, UK;National Institute for Biological Standards and Control, Potters Bar, Herts, UK;Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Odonto – Stomatology, USTTB, BP 1805, Bamako, Mali;Malaria Research and Training Centre, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Odonto – Stomatology, USTTB, BP 1805, Bamako, Mali;Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden;Wellcome Trust Centre for Human Genetics, University of Oxford, OX3 7BN, Oxford, UK;Wellcome Trust Sanger Institute, Hinxton, Cambs, UK;

关键词: Genetic association study;    G6PD deficiency;    Plasmodium falciparum;    Malaria;    Fulani;    Dogon;    Mali;   

DOI  :  10.1186/1475-2875-13-270

 received in 2014-01-26, accepted in 2014-07-02,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundGlucose-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.MethodsA 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.ResultsIt 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.ConclusionsThe 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.

【 授权许可】

CC BY   
© Maiga et al.; licensee BioMed Central Ltd. 2014