A61‐C haptoglobin gene promoter polymorphism and protection from malaria in Gambian children

• Published in: The FASEB journal 2007-04, Vol.21 (5), p.A164-A164
• Main Authors: Cox, Sharon Elizabeth, Doherty, Conor, Atkinson, Sarah Helen, Nweneka, Chidi Victor, Ghattas, Hala, Fulford, Tony, Rockett, Kirk, Kwiatkowski, Dominic, Prentice, Andrew
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.21.5.A164-b

The objective of this study was to determine if polymorphisms in haptoglobin (Hp), an acute phase protein that clears haemoglobin from haemolysis of red cells, are associated with susceptibility to malaria. In a cohort study, risk of a clinical malarial episode during the malarial transmission season was assessed in 598 Gambian children aged 12–72 months. We report for the first time that the major haplotype for the A‐61C mutant allele in the promoter region of Hp is associated with protection from malaria infection (>500 parasites/ul & temp >37.5°C; OR=0.66; [95%CI 0.44–0.99] p=0.043) and blinded clinical diagnosis of malaria (OR=0.48; [95%CI 0.30–0.78]; p=0.003). The level of protection was similar to that observed with sickle cell trait, known to be protective against malaria. Previously, functional polymorphisms of Hp, coded by the co‐dominant alleles Hp1 and Hp2, have been variously associated with several infectious diseases, including malaria. We propose that these conflicting results may be explained by differences in population prevalence of the A‐61C SNP, which we found to be highly associated with the Hp2 allele. We confirm in vitro studies showing that the A‐61C SNP is associated with decreased Hp protein expression, manifested as decreased circulating levels of Hp ‐ independent of Hp phenotype, thus suggesting a possible mechanism of protective action against malaria.