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Frequency of RANTES gene polymorphisms and their association with incidence of malaria: a longitudinal study on children in Iganga district, Uganda
Makerere Univ, Coll Hlth Sci, Sch Biomed Sci, Kampala, 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.
Makerere Univ, Coll Hlth Sci, Sch Biomed Sci, Kampala, Uganda.;Islamic Univ Uganda IUIU, Fac Hlth Sci, Habib Med Sch, Kampala, Uganda..
2015 (English)In: Malaria Journal, ISSN 1475-2875, Vol. 14, 341Article in journal (Refereed) Published
Abstract [en]

Background: The severity and outcome of malaria is influenced by host immunity in which chemokines such as Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES) play an important role. Previous studies show that variations in the RANTES gene affect RANTES protein production, hence altering host immunity. In this study, the relationship between presence of mutations in RANTES and incidence of malaria in a cohort of children living in a malaria-endemic area of Uganda was determined. Methods: This was a longitudinal study comprising of 423 children aged between 6 months and 9 years, who were actively followed up for 1 year. Malaria episodes occurring in the cohort children were detected and the affected children treated with national policy drug regimen. Mutations in the RANTES gene were determined by PCR-RFLP method and their frequencies were calculated. A multivariate negative binomial regression model was used to estimate the impact of RANTES mutations on malaria incidence. In all statistical tests, a P-value of <0.05 was considered as significant. Results: The frequencies of the -403A and In1.1C allele were 53.7 and 19.2 %, respectively. No mutations were found at the -28 locus. After adjustment of incidence rates for age, blood group, insecticide-treated bed net (ITN) use, malaria history and the sickle cell trait, 1n1.1T/C heterozygotes and homozygotes showed a non-significant trend towards higher incidence rates compared to wild-type individuals (IRR = 1.10; P = 0.55 and IRR = 1.25; P = 0.60, respectively). Similarly, there was no significant difference in malaria incidence rates between RANTES -403G/A heterozygotes or homozygotes and those without mutations (IRR = 1.09; P = 0.66 and IRR = 1.16; P = 0.50, respectively). No relation was seen between RANTES polymorphisms, baseline parasite densities and the time to first re-infection after administration of anti-malaria drugs. Conclusions: This study showed that the -403A mutation occurs in nearly half of the study population and the In1.1C allele occurs in one in every four children. Despite the high frequency of these mutations, there was no clear association with malaria incidence. Other studies evaluating more markers, that could potentially modulate RANTES gene transcription alongside other genetic modifiers of malaria susceptibility, may provide further explanations to these less dramatic findings.

Place, publisher, year, edition, pages
2015. Vol. 14, 341
Keyword [en]
RANTES gene polymorphisms, Plasmodium falciparum malaria, Incidence
National Category
Microbiology in the medical area
URN: urn:nbn:se:uu:diva-263431DOI: 10.1186/s12936-015-0875-0ISI: 000360605100002PubMedID: 26341782OAI: diva2:859558
EU, FP7, Seventh Framework Programme, 242095 (EVIMALAR)Sida - Swedish International Development Cooperation Agency
Available from: 2015-10-07 Created: 2015-09-30 Last updated: 2015-10-07Bibliographically approved

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