Haptoglobin: a major susceptibility gene for diabetic cardiovascular disease.

Haptoglobin polymorphism Haptoglobin is a serum protein for which there are two common alleles in humans, denoted 1 and 2 [1]. The genotype of an individual may therefore be described as being Hp 1-1 (homozygous for the 1 allele), Hp 2-2 (homozygous for the 2 allele), or Hp 2-1 (the heterozygote). The haptoglobin gene locus on chromosome 16q22 has 5 exons encoding the 1 allele or 7 exons encoding the 2 allele [2]. The 2 allele appears to have been generated from the 1 allele by an intragenic duplication event of exons 3 and 4. Hp typing of over 100,000 individuals over the past 35 years has shown considerable geographic and ethnic variation in the frequencies of the two alleles [2]. In Israel, the two alleles are in a balanced polymorphism with approximately 30% of the alleles being type 1 and 70% type 2, thus 9% of the Israeli population is Hp 1-1, 49% is Hp 2-2 and 42% is Hp 2-1 [2]. This allele frequency distribution is quite similar to that found in Europe and the United States. The distribution of these two alleles in individuals with diabetes is not different to that in the general population [3].