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

Malaria Journal

Research

Göte Swedberg¹  Fred Kironde²  Catherine Nassozi Lwanira³  Mark Kaddumukasa⁴ 

[1] Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden;Habib Medical School, Faculty of Health Sciences, Islamic University in Uganda (IUIU), Kampala Campus, Kampala, Uganda;School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda;School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda;

关键词: Human gene polymorphisms;    Plasmodium falciparum;    Incidence;   

DOI  :  10.1186/s12936-017-1970-1

 received in 2017-04-05, accepted in 2017-08-03,  发布年份 2017

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s) 2017