Prevalence of polymorphisms in glucose-6-phosphate dehydrogenase, sickle haemoglobin and nitric oxide synthase genes and their relationship with incidence of uncomplicated malaria in Iganga, Uganda

Catherine Nassozi Lwanira,Mark Kaddumukasa,Göte Swedberg,Fred Kironde

doi:10.1186/s12936-017-1970-1

Catherine Nassozi Lwanira, Mark Kaddumukasa + Show 2 more

Open Access

https://doi.org/10.1186/s12936-017-1970-1

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Abstract

BackgroundHost genetics play an important role in Plasmodium falciparum malaria susceptibility. However, information on host genetic factors and their relationships with malaria in the vaccine trial site of Iganga, Uganda is limited. The main objective of this study was to determine the prevalence of selected host genetic markers and their relationship to malaria incidence in the vaccine trial site of Iganga, Uganda. In a 1-year longitudinal cohort study, 423 children aged below 9 years were recruited and their malaria episodes were investigated. Host genetic polymorphisms were assessed by PCR–RFLP, haemoglobin electrophoresis and DNA sequencing. Using a multivariate negative binomial regression model, estimates of the impact of human genetic polymorphisms on malaria incidence were performed. In all statistical tests, a P value of <0.05 was considered as significant.ResultsThe prevalences of sickle cell haemoglobin trait, G6PD c.202 G>A (rs 1050828) and NOS2 −954 G>C (rs 1800482) variants were 26.6, 22.7 and 17.3%, respectively. Inducible nitric oxide synthase 2 (NOS2 −954 G>C; rs 1800482) heterozygosity was associated with lower incidence of malaria in all age groups {Adjusted incident rates ratio (aIRR) 0.59; 95% CI [0.386–0.887]; P = 0.012)}. About 4% of study subjects had co-existence of sickle cell Hb trait and G6PD deficiency. Sickle cell Hb heterozygotes (Hb AS) aged less than 1 year experienced significantly more malaria episodes annually than children with normal haemoglobin (Hb AA) {aIRR = 1.98; 95% CI [1.240–3.175]; P = 0.004}. There was no significant influence of the sickle cell trait on malaria incidence among older children of 1–9 years.ConclusionsMutation (NOS2 −954 G>C; rs 1800482) of nitric oxide synthase 2 gene promoter was associated with a lower incidence of acute malaria. The normal haemoglobin (wild genotype; HbAA) was associated with reduced malaria incidence rates during the first year of life. More understanding of the interplay between host genetics and malaria susceptibility is required.

Highlights

Host genetics play an important role in Plasmodium falciparum malaria susceptibility
The sickle cell trait and glucose-6-phosphate dehydrogenase (G6PD) deficiency stand out among other host genetic markers reported in genome wide association and multicentre studies [1,2,3]
G6PD deficiency affects over 400 million people globally, 15-30% of whom are found in sub Saharan Africa [12, 13]

Summary

Introduction

Host genetics play an important role in Plasmodium falciparum malaria susceptibility. The main objective of this study was to determine the prevalence of selected host genetic markers and their relationship to malaria incidence in the vaccine trial site of Iganga, Uganda. The sickle cell trait and glucose-6-phosphate dehydrogenase (G6PD) deficiency stand out among other host genetic markers reported in genome wide association and multicentre studies [1,2,3]. Many of the earlier studies were largely case–control and examined effects of G6PD deficiency on the risk of severe malaria but not the incidence of uncomplicated malaria. These studies were done in other populations outside Uganda. Two longitudinal studies that were done in Uganda [20] and Gabon [21] found an increase in the malaria incidence rates among female heterozygotes

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