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provided by Cronfa at Swansea University INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY
Haptoglobin: a review of the major allele frequencies worldwide and their association with diseases KYMBERLEY CARTER*, MARK WORWOOD
Department of Haematology, SUMMARY School of Medicine, Cardiff University, Heath Park, Cardiff, UK Haptoglobin (Hp) is a plasma a2-glycoprotein which binds free haemoglobin, thus preventing oxidative damage. The complex is Correspondence: Prof. Mark Worwood, Department rapidly removed from the circulation by a specific receptor (CD163) of Haematology, School of Medi- found on macrophages. Three major subtypes, Hp1-1, Hp2-1 and cine,CardiffUniversity,HeathPark, Hp2-2 are the product of two closely related genes HP1 and HP2.The Cardiff CF14 4XN, UK; E-mail: frequency of the HP1 and HP2 genes varies worldwide depending on [email protected] racial origin: the HP1frequency varying from about 0.07 in parts of 1 *Present address: Centre for Health India to over 0.7 in parts of West Africa and South America. Both HP Information Research and Evalua- and HP2 have been linked to susceptibility to various diseases. Such tion (CHIRAL), School of Medicine, associations may be explained by functional differences between the University of Wales, Swansea, UK. subtypes in the binding of Hb and its rate of clearance from the plasma. doi:10.1111/j.1365-2257.2007.00898.x However, there are also corresponding negative reports for disease associations. The conflicting evidence on disease association and the Received 29 March 2006; accepted for publication 5 January 2007 lack of association between disease and particular populations, despite thewiderangeofHP1 and HP2 gene frequencies across the world, may Keywords indicate that any associations are marginal. Haptoglobin, haptoglobin type, population distribution, disease association, haem breakdown, iron metabolism
1959). Haptoglobin binds oxygenated, free haemoglo- HAPTOGLOBIN STRUCTURE AND FUNCTION bin with a very high affinity of approximately ) Polonovski and Jayle (1940) first described a protein 1 · 10 15 mol/l (Okazaki, Yanagisawa & Nagai, 1997). with haemoglobin binding properties, which they Free haemoglobin can be harmful to the body, pro- later designated ‘haptoglobin’, from the Greek word moting the accumulation of hydroxyl radicals via the 2+ 3+ ) haptein – to bind. Fenton reaction (H2O2 +Fe fi Fe +OH + OH),
Haptoglobin (Hp) is a plasma a2-glycoprotein syn- resulting in oxidative tissue damage (Sadrzadeh et al., thesized primarily by hepatocytes (Putnam, 1975). 1984). Once irreversibly bound to haptoglobin, free Synthesis is stimulated by infection or inflammation haemoglobin loses its oxidizing ability (Sadrzadeh (the acute phase response). After release into the cir- et al., 1984; Gutteridge, 1987). The haptoglobin– culation it has a half-life of 2–4 days (Garby & Noyes, haemoglobin (Hp–Hb) complex is removed from the