Acta Tropica 126 (2013) 127–131 Contents lists available at SciVerse ScienceDirect Acta Tropica journa l h o me pa g e: www.elsevier.com/locate/actatropica Haptoglobin phenotypes and iron status in children living in a malaria endemic area of Kenyan coast Alice M. Nyakeriga a,b,c,∗ , Marita Troye-Blomberg b a Texas Tech University, Department of Biomedical Sciences, El Paso, TX, USA b Stockholm University, Department of Immunology Wenner-Gren Institute, Stockholm, Sweden c KEMRI/Wellcome Trust Programme, Centre for Geographic Medicine Research, Coast, Kilifi District Hospital, Kilifi, Kenya a r t i c l e i n f o Article history: Received 27 September 2012 Received in revised form 31 January 2013 Accepted 1 February 2013 Available online 13 February 2013 Keywords: Malaria Iron status Haptoglobin Genetic factors a b s t r a c t Malaria infection may be affected by host genetic factors as well as nutritional status. Iron status and the phenotype of haptoglobin, a heme-binding acute phase reactant may be determinants of malaria parasitemia. A combination of cross sectional studies and longitudinal follow-up were used to describe the association between iron status, C-reactive protein, malaria infections and host genetic factors including; haptoglobin (Hp) phenotypes, in children below 9 years in a malaria endemic area in Coastal Kenya. The prevalence of 0.45 and 0.41, respectively for Hp 1-1 and Hp 2-1 phenotypes was significantly higher than 0.14 for Hp 2-2 phenotype (n = 162). Children with Hp 2-2 phenotype showed significantly higher iron storage compared to those with Hp 1-1 and Hp 2-1 phenotypes when children with malaria parasites and high C-reactive protein (>9 mg/L) were excluded from the analysis. There were no significant differences in malaria parasite densities among Hp phenotypes but children with Hp 2-2 had lower number of clinical malaria episodes (P = 0.045). Taken together, this study shows that the presence of malaria may complicate the interpretation of iron status in children based on their Hp-phenotypes. Further studies will be required to address possible interactions among the various genetic factors and iron status in a malaria endemic setting. Published by Elsevier B.V. 1. Introduction Iron status in man is influenced by both environmental and genetic factors. Molecular variation of haptoglobin (Hp), a plasma protein, is one of the genetic factors known to influence iron status (Langlois et al., 2000). Hp is a type II acute phase protein secreted by hepatocytes during an inflammatory reaction. In humans, Hp is characterized by a genetic polymorphism with three structurally different phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2) which are the result of the expression of two different alleles; Hp1 and Hp2, of the Hp gene located on chromosome 16q22 (Langlois and Delanghe, 1996). Hp is responsible for the removal of free hemoglobin (Hb) in the form of Hp–Hb complexes from the circulation with subsequent reduction in Hb loss through the kidney. Consequently, the kidney is protected against damage and iron recycling is permitted. Hp 2-2 is associated with higher serum iron and transferrin saturation lev- els as compared to other phenotypes reflecting a relative increase in the iron transport (Delanghe and Langlois, 2002). For example, Hp 2-2 male Caucasians have been characterized with larger iron ∗ Corresponding author at: Department of Biomedical Sciences, El Paso, TX, USA. Tel.: +1 915 783 5227; fax: +1 915 783 5223. E-mail address: alice.nyakeriga@ttuhsc.edu (A.M. Nyakeriga). stores as evidenced by higher serum ferritin levels compared to their Hp 1-1 and Hp 2-1 counterparts (Langlois et al., 2000). Haptoglobin phenotypes differ in their biological activities and have been associated with resistance or susceptibility to infec- tious diseases (Langlois and Delanghe, 1996). Iron withholding is an important example of nutritional immunity playing a role in the defense against infectious diseases (Pradines et al., 2003; Weiss et al., 1994, reviewed in Gordeuk et al., 2001; Weinberg, 2009). Haptoglobin acts as a natural bacteriostatic agent by pre- venting the utilization of hemoglobin by pathogenic bacteria, which require iron for their growth. In malaria endemic areas, Hp 1-1 but not Hp 2-2 with disease severity (Elagib et al., 1998), per- haps through iron withholding related mechanisms. While the role of iron in malaria susceptibility remains controversial, there is evidence that iron deficiency protects against disease (reviewed in Oppenheimer, 2001). We previously observed an association between iron deficiency and protection against malaria infection in a cohort of children living on the coast of Kenya (Nyakeriga et al., 2004). Given the existing association between haptoglobin polymorphism and iron status or malaria susceptibility, there was need to investigate the interaction of these three conditions in our cohort of children. We subsequently investigated the effect of hap- toglobin polymorphism on biochemical markers of iron and malaria infection. 0001-706X/$ – see front matter. Published by Elsevier B.V. http://dx.doi.org/10.1016/j.actatropica.2013.02.004