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HAPTOGLOBIN LEVELS ARE ASSOCIATED WITH HAPTOGLOBIN GENOTYPE AND ⁺-THALASSEMIA IN A MALARIA-ENDEMIC AREA

Haptoglobin (Hp) is an acute phase protein that removes free hemoglobin (Hb) released during hemolysis. Hp has also been shown to be toxic for malaria parasites. ⁺-Thalassemia is a hemoglobinopathy that results in subclinical hemolytic anemia. ⁺-Thassemia homozygosity confers protection against severe malarial disease by an as yet unidentified mechanism. Hp levels were measured in a serial cross-sectional survey of children in Madang Province, Papua New Guinea (PNG). Hp levels were related to age, Hp genotype, Hb levels, parasitemia, splenomegaly, and ⁺-thalassemia genotype. Surprisingly, children who were homozygous for ⁺ -thalassemia had significantly higher levels of Hp than did heterozygotes, after controlling for relevant confounders. We suggest that this is the result of either reduced mean cell Hb associated with ⁺ -thalassemia homozygosity or an elevated IL-6–dependent acute phase response.

Received August 20, 2005. Accepted for publication February 2, 2006.

Acknowledgments: For field work, we are indebted to the staff of the Papua New Guinea Institute of Medical Research and to the Amele community for agreeing to take part in this study. Ruth Ripley gave advice on statistical analysis. Clare Watkinson and Sam Mason gave technical support, and the authors thank Michael Alpers and Sir David Weatherall for long-term contribution to -thalassemia research in Melanesia.

Financial support: This work was funded by the Wellcome Trust and the European Community (E.C.Grant IC18-CT98-0359).

^* Address correspondence to Karen P. Day, Department of Medical Parasitology, New York University School of Medicine, 341 East 25th Street, New York, NY 10010. E-mail: karen.day{at}med.nyu.edu

Authors’ addresses: Heather Imrie and Jennifer C.C. Hume, Peter Medawar Building for Pathogen Research, Department of Zoology, South Parks Road, Oxford University, Oxford, OX1 3SY, United Kingdom, E-mails: heather.imrie{at}medawar.ox.ac.uk and Jennifer.hume{at}medawar.ox.ac.uk. Freya J.I. Fowkes and K.P. Day, Department of Medical Parasitology, New York University School of Medicine, 341 East 25th Street, New York, NY 10010, Telephone: 212-263-6800, Fax: 212-263-8116, E-mails: frey.fowkes{at}med.nyu.edu and Karen.day{at}med.nyu.edu. Pascal Michon and Livingstone Tavul, Papua New Guinea Institute of Medical Research, P.O. Box 378, Madang 511, Papua New Guinea, Telephone: 675-852-2909, Fax: 675-852-3289, E-mails: pmichon{at}datec.net.pg and livingstone.tavul{at}pngimr.org.pg. Karen P. Piper, CRUK Institute for Cancer Studies, University of Birmingham, Vincent Drive, Edgbaston, Birmingham, B15 2TT, E-mail: k.p.piper{at}bham.ac.uk. John C. Reeder, Papua New Guinea Institute of Medical Research, P.O. Box 60, Goroka, EHP 441, Papua New Guinea, E-mail: john.reeder{at}pngimr.org.pg.

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