Haptoglobin gene diversity and incidence of uncomplicated malaria among children in Iganga, Uganda

Abstract

Background Haptoglobin (Hp) is an acute phase protein that takes part in systemic regulation of haem during Plasmodium falciparum infections. Numerous genotypes of haptoglobin have been reported in malaria endemic populations. In this study, the relationship between haptoglobin genotypes and incidence of uncomplicated malaria in a cohort of children living in a malaria-endemic area of Uganda was determined. Methods This is an extension of a longitudinal study comprising of 423 children aged between six months and nine years, who were actively followed up for one year. Malaria episodes occurring in the cohort children were detected and the affected children treated with national policy drug regimen. Haptoglobin genotypes were determined by an allele-specific PCR method and their frequencies were calculated. A multivariate negative binomial regression model was used to estimate the impact of haptoglobin genotypes on incidence of uncomplicated malaria in the children’s cohort. In all statistical tests, a P–value of < 0.05 was considered as significant. Results The prevalence of the Hp 1–1, Hp 2–1 and Hp 2–2 genotypes in the children’s cohort was 41%, 36.2% and 22.9%, respectively. The overall frequency for the Hp 1 allele was 59%, while Hp 2 allele occurred at a frequency of 41%. After adjustment of incidence rates for age, insecticide treated bed net (ITN) use and malaria history, the incidence of uncomplicated malaria for children carrying the Hp 2–2 genotype and those with the Hp 2–1 genotype was statistically similar (P = 0.41). Also, no difference in the incidence of uncomplicated malaria was observed between children carrying the Hp 1–1 genotype and those having the Hp 2–1 genotype (P = 0.84) or between Hp 2–2 Vs Hp 1–1 genotypes (P = 0.50). Conclusions This study showed that the Hp 1–1 and Hp 2–1 genotypes each occur in nearly 4 in 10 children and the Hp 2–2 genotype occurs in 2 of every 10 children. No association with incidence of uncomplicated malaria was found. Additional studies of influence of haptoglobin genotypes on P. falciparum malaria severity are needed to understand the role of these genotypes in malarial protection.