Haptoglobin

Alternative Names

  • HP
  • Haptoglobin, Alpha Polypeptide
  • Haptoglobin, Beta Polypeptide
  • BP

Associated Diseases

Type 2 Diabetes Mellitus
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OMIM Number

140100

NCBI Gene ID

3240

Uniprot ID

P00738

Length

6,551 bases

No. of Exons

7

No. of isoforms

2

Protein Name

Haptoglobin

Molecular Mass

45205 Da

Amino Acid Count

406

Genomic Location

chr16:72,054,504-72,061,054

Gene Map Locus
16q22.2

Description

This gene encodes a preproprotein, which is processed to yield both alpha and beta chains, which subsequently combine as a tetramer to produce haptoglobin. Haptoglobin functions to bind free plasma hemoglobin, which allows degradative enzymes to gain access to the hemoglobin, while at the same time preventing loss of iron through the kidneys and protecting the kidneys from damage by hemoglobin. Mutations in this gene and/or its regulatory regions cause ahaptoglobinemia or hypohaptoglobinemia. This gene has also been linked to diabetic nephropathy, the incidence of coronary artery disease in type 1 diabetes, Crohn's disease, inflammatory disease behavior, primary sclerosing cholangitis, susceptibility to idiopathic Parkinson's disease, and a reduced incidence of Plasmodium falciparum malaria. The protein encoded also exhibits antimicrobial activity against bacteria. A similar duplicated gene is located next to this gene on chromosome 16. Multiple transcript variants encoding different isoforms have been found for this gene. From RefSeq]

Molecular Genetics

Most of the haptoglobin is synthesized in the liver. Other sites of production include skin, lungs, and kidneys. The mature protein is a tetramer, consisting of two alpha and two beta chains, connected by disulfide bridges. The beta chain of the protein binds the hemoglobin tetramer. Both the alpha and beta chains are protelolytically processed from the same precursor polypeptide. This precursor molecule contains a signal sequence, at least one Sushi domain and a trypsin domain. The Sushi domain belongs to the alpha chain, whereas the trypsin domain is part of the beta chain. The active site residues of the trypsin domain are not conserved, and therefore, have no enzymatic activity.

Two allelic variants of the haptoglobin gene, Hp1 and Hp2, are commonly seen. These two alleles result in three major phenotypes: Hp 1-1, Hp 2-1, and Hp 2-2. According to most reports, a great amount of variability is seen in the distribution of Hp types in different populations.

Epidemiology in the Arab World

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Other Reports

Saudi Arabia

Awadallah et al (2001) conducted a study on 1002 (696 males, and 306 females) unrelated Saudis, residing in the Asir region of Southern Saudi Arabia, in order to understand the distribution of Hp types in the region. Sera were collected from these individuals, and Hp-Hb complexes separated from them. Hp typing was done using vertical PAGE (7%). Serum Hp concentration was determined using a commercial kit. Results showed that among the population, Hp 2-1 was the most common allele with a frequency of 0.487 (0.532 in males, 0.386 in females). The least common allele was Hp 1-1, at a frequency of 0.183 (0.185 in males, 0.176 in females). This distribution was found to be in agreement with the expectations of the Hardy Weinberg Equilibrium, and similar to that seen in Europeans, Caucasians, and Asians, but dissimilar to that observed in Polynesians, Australians, and Blacks. Hp 0-0 was found in the population at a frequency of 0.058 (.053 in males, and .069 in females). All individuals with Hp 0-0 were asymptomatic. No statistically significant variations were detected between the male and female populations in the distribution of the Hp types. On the other hand, serum Hp concentration was found to vary greatly between the sexes. The serum Hp values of Hp 2-1 and Hp 1-1 females were significantly higher than those of males. In males, the serum from Hp 2-2 males was found to contain more normal Hp than Hp 2-1 or Hp 1-1 individuals. Similarly, Hp 2-1 females also had significantly higher normal Hp values than Hp 2-2 females. Awadallah et al. (2001) were of the opinion that the establishment of the Hp allele frequencies would facilitate the future analysis of the ethno-genetic relationships among population groups in Saudi Arabia.

[Awadallah S, Hamad M, Kadumi O. Phenotype distribution and normal values of haptoglobin in Asir region of Southern Saudi Arabia. Bahrain Med Bull. 2001; 23(1):8-11]

United Arab Emirates

In a study on 271 Emirati patients with Type 2 DM and 215 healthy controls, Al-Safar et al. (2015) found the HP-2 allele to be significantly associated with the disease condiiton only in an autosomal dominant model. 

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