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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
Makerere Univ, Coll Hlth Sci, Sch Biomed Sci, Kampala, Uganda..
Islamic Univ Uganda IUIU, Fac Hlth Sci, Habib Med Sch, Kampala Campus, Uganda..
Makerere Univ, Coll Hlth Sci, Sch Med, Kampala, Uganda..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
2017 (English)In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 16, article id 322Article in journal (Refereed) Published
Abstract [en]

Background: Host 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. Results: The 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. Conclusions: Mutation (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.

Place, publisher, year, edition, pages
2017. Vol. 16, article id 322
Keyword [en]
Human gene polymorphisms, Plasmodium falciparum malaria, Incidence
National Category
Infectious Medicine Microbiology in the medical area
Identifiers
URN: urn:nbn:se:uu:diva-332663DOI: 10.1186/s12936-017-1970-1ISI: 000407839500001OAI: oai:DiVA.org:uu-332663DiVA, id: diva2:1153865
Funder
EU, FP7, Seventh Framework Programme, 242095
Available from: 2017-10-31 Created: 2017-10-31 Last updated: 2018-01-13Bibliographically approved

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