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

[alpha-thalassemia]

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 : Hp 2 -1 was associated with the greatest protection against severe malaria and Hp 2 -2 with the greatest risk . Meta -analysis of the current and published studies suggests that Hp 2 -2 is associated with increased risk of severe malaria compared with Hp 2 -1 . We found a significant interaction between Hp genotype and α (+)thalassemia in predicting risk of severe malaria : Hp 2 -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 Hp 2 -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 .

Diseases
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Diseases presenting "increased risk of severe malaria" symptom

alpha-thalassemia

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