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

نویسندگان

  • Sarah H Atkinson
  • Sophie M Uyoga
  • Emily Nyatichi
  • Alex W Macharia
  • Gideon Nyutu
  • Carolyne Ndila
  • Dominic P Kwiatkowski
  • Kirk A Rockett
  • Thomas N Williams
چکیده

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.

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منابع مشابه

Epistasis between the haptoglobin common variant and athalassemia influences risk of severe malaria in Kenyan children

Department of Paediatrics, Oxford University Hospitals National Health Service Trust, University of Oxford, and Oxford University Clinical Academic Graduate School, Oxford, United Kingdom; Kenya Medical Research Institute/Wellcome Trust Research Programme, Centre of Geographic Medicine Research-Coast, Kilifi District Hospital, Kilifi, Kenya; Wellcome Trust Centre for Human Genetics, University ...

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عنوان ژورنال:
  • Blood

دوره 123 13  شماره 

صفحات  -

تاریخ انتشار 2014