Distribution of haptoglobin subtypes in Greeks.

Human haptoglobin, the serum haemoglobinbinding protein, can be differentiated into three common phenotypes (Hp i-i, Hp 2-I, and Hp2-2) by means of starch gel electrophoresis at pH 8-6 (Smithies, 1955). These differences were thought to be determined by a pair of allelic genes Hp" and Hp2 (Smithies and Walker, I955, I956). However, chemical reduction of purified haptoglobin followed by electrophoresis in starch gels, prepared in formic acid buffer containing 8M urea, enabled Connell, Dixon, and Smithies (I962) and Smithies, Connell, and Dixon (i962a) to classify individuals of phenotype i-i into three subphenotypes, HpiF-iF, HpiF-iS, and HpiSiS. These three subphenotypes are controlled by two alleles, HplF and HplS. People of haptoglobin phenotype 2-I could also subtyped in a similar fashion into HP2-IF or HP2-IS. Thus, a series of six phenotypes in the haptoglobin system can now be recognized (HpIF-iF, iF-iS, iS-iS, 2-IF, 2-IS, and 2-2). Chemical reduction of purified haptoglobin separates the protein into two polypeptide chains. Only the a chain has been found to vary in the six phenotypes, and the allele designations are referred to the a chain. The 13 chain appears to be unaffected by the genotype of the Hp locus (Smithies, Connell, and Dixon, I962b). Chemical studies on the a chains (Smithies et al., i962b; Dixon, Smithies, and Connell, I962) have disclosed a single amino acid difference between the acs and the alF chain. The a2 chain has characteristics of both als and alF chains and appears to represent the unequal fusion of two al chains. However, two a2 chain variants were found in a population of Indians from Brazil (Nance and Smithies, I963). Although the distribution of the three common phenotypes in various populations is well known, very little information on the distribution of the subtypes of haptoglobin i-i is available. Two