The role of haptoglobin genotypes in Chagas disease.

Ninomar Mundaray Fernández,Mercedes Fernández-Mestre

doi:10.1155/2014/793646

Ninomar Mundaray Fernández, Mercedes Fernández-Mestre

Open Access

https://doi.org/10.1155/2014/793646

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Abstract

Although the number of people infected with T. cruzi is on the rise, host genetic and immune components that are crucial in the development of the Chagas disease have been discovered. We investigated the frequency of polymorphisms in the gene encoding haptoglobin of patients with chronic Chagas disease. The results suggest that while the HP1-1 genotype may confer protection against infection and the development of chronic Chagas disease due to the rapid metabolism of the Hp1-1-Hb complex and its anti-inflammatory activity, the presence of HP2-2 genotype may increase susceptibility towards a chronic condition of the disease due to a slow metabolism of the Hp2-2-Hb complex, lower antioxidant activity, and increased inflammatory reactivity, which lead to cell damage and a deterioration of the cardiac function. Finally, correlations between HP genotypes in different age groups and cardiac manifestations suggest that HP polymorphism could influence the prognosis of this infectious disease. This study shows some of the relevant aspects of the haptoglobin gene polymorphism and its implications in the T. cruzi infection.

Highlights

American trypanosomiasis is recognized by the World Health Organization (WHO) as one of the 13 major neglected diseases in the tropical world constituting a serious social and economic impact in several countries, especially in Latin America
The haptoglobin polymorphism is composed of two HP1 and HP2 codominant alleles resulting in three major HP genotypes HP1-1, HP2-2, and HP2-1 corresponding to proteins of different structural and functional properties [3]
The HP2-2 genotype had a significantly higher frequency in chagasic patients with mild and severe cardiac symptoms (Groups B and C, resp.), suggesting that this genotype confers susceptibility to the cardiac disease characteristic of Chagas disease. This opinion was confirmed in comparisons between symptomatic and asymptomatic Chagas infected patients. To explain this susceptibility promoted by the HP2-2 genotype, we considered two important aspects: (1) trypanosomatids requiring iron for vital processes including DNA replication and mitochondrial respiration; the heme biosynthetic pathway is completely absent in T. cruzi, so the iron must be obtained from the host [16]; (2) the structural and functional characteristics of the molecule Hp 2-2

Summary

Introduction

American trypanosomiasis is recognized by the World Health Organization (WHO) as one of the 13 major neglected diseases in the tropical world constituting a serious social and economic impact in several countries, especially in Latin America. Haptoglobin (Hp) is an acute-phase protein synthesized mainly by the liver during inflammatory processes whose main function is to remove the free hemoglobin (Hb) by forming Hp-Hb complexes that are eliminated primarily by monocytes/macrophages. Haptoglobin possesses anti-inflammatory and antioxidant properties [2]. The haptoglobin polymorphism is composed of two HP1 and HP2 codominant alleles resulting in three major HP genotypes HP1-1, HP2-2, and HP2-1 corresponding to proteins of different structural and functional properties [3]. The Hp 1-1 phenotype has been associated with high plasma concentrations [4] and an increased antioxidant capacity [5], affinity for hemoglobin [4], and clearance of Hp-Hb (CD163-mediated) [6] regarding Hp phenotype 2-2. The Hp 1-1 phenotype induces greater amounts of antiinflammatory interleukins than the Hp 2-2 phenotype [7]

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