Epistasis between the haptoglobin common variant and α+thalassemia influences risk of severe malaria in Kenyan children

Atkinson, S; Uyoga, S; Nyatichi, E; Macharia, A; Nyutu, G; Ndila, C; Kwiatkowski, D; Rockett, K; Williams, T

Journal article

Epistasis between the haptoglobin common variant and α+thalassemia influences risk of severe malaria in Kenyan children

Abstract:: Haptoglobin (Hp) scavenges free hemoglobin following malaria-induced hemolysis. Few studies have investigated the relationship between the common Hp variants and the risk of severe malaria, and their results are inconclusive. We conducted a case-control study of 996 children with severe Plasmodium falciparum malaria and 1220 community controls and genotyped for Hp, hemoglobin (Hb) S heterozygotes, and α(+)thalassemia. Hb S heterozygotes and α(+)thalassemia homozygotes were protected from severe malaria (odds ratio [OR], 0.12; 95% confidence interval [CI], 0.07-0.18 and OR, 0.69; 95% CI, 0.53-0.91, respectively). The risk of severe malaria also varied by Hp genotype: Hp2-1 was associated with the greatest protection against severe malaria and Hp2-2 with the greatest risk. Meta-analysis of the current and published studies suggests that Hp2-2 is associated with increased risk of severe malaria compared with Hp2-1. We found a significant interaction between Hp genotype and α(+)thalassemia in predicting risk of severe malaria: Hp2-1 in combination with heterozygous or homozygous α(+)thalassemia was associated with protection from severe malaria (OR, 0.73; 95% CI, 0.54-0.99 and OR, 0.48; 95% CI, 0.32-0.73, respectively), but α(+)thalassemia in combination with Hp2-2 was not protective. This epistatic interaction together with varying frequencies of α(+)thalassemia across Africa may explain the inconsistent relationship between Hp genotype and malaria reported in previous studies.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Atkinson, S., Uyoga, S., Nyatichi, E., Macharia, A., Nyutu, G., Ndila, C., Kwiatkowski, D., Rockett, K., & Williams, T. (2014). Epistasis between the haptoglobin common variant and α+thalassemia influences risk of severe malaria in Kenyan children. Blood, 123(13), 2008–2016.

MLA Style

Atkinson, S., et al. “Epistasis between the Haptoglobin Common Variant and α+Thalassemia Influences Risk of Severe Malaria in Kenyan Children.” Blood, vol. 123, no. 13, American Society of Hematology, 2014, pp. 2008–16.

Chicago Style

Atkinson, S, S Uyoga, E Nyatichi, A Macharia, G Nyutu, C Ndila, D Kwiatkowski, K Rockett, and T Williams. 2014. “Epistasis between the Haptoglobin Common Variant and α+Thalassemia Influences Risk of Severe Malaria in Kenyan Children.” Blood 123 (13): 2008–16.
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