Haptoglobin: a review of the major allele frequencies worldwide and their association with diseases

Haptoglobin (Hp) is a plasma alpha(2)-glycoprotein which binds free haemoglobin, thus preventing oxidative damage. The complex is rapidly removed from the circulation by a specific receptor (CD163) found on macrophages. Three major subtypes, Hpl-1, Hp2-1 and Hp2-2 arc the product of two closely related genes HP1 and HP2. The frequency of the HP1 and HP2 genes varies worldwide depending on racial origin: the HP1 frequency varying from about 0.07 in parts of India to over 0.7 in parts of West Africa and South America. Both HP1 and HP2 have been linked to susceptibility to various diseases. Such associations may be explained by functional differences between the subtypes in the binding of Hb and its rate of clearance from the plasma. However, there are also corresponding negative reports for disease associations. The conflicting evidence on disease association and the lack of association between disease and particular populations, despite the wide range of HP1 and HP2 gene frequencies across the world, may indicate that any associations are marginal.