Polymorphism of human haptoglobin and its clinical importance

Wobeto, Vânia Peretti de Albuquerque; Zaccariotto, Tânia Regina; Sonati, María de Fátima

doi:10.1590/s1415-47572008000400002

Cited by 56 publications

(50 citation statements)

References 169 publications

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“…In humans, the Hp locus is on the long arm of chromosome 16 (16q22) and is polymorphic, with two main alleles (HP1 and HP2) resulting in three distinct genotypes/phenotypes (Hp1-1, Hp2-1 and Hp2-2) 9,10 . The Hp proteins have distinct biochemical and biophysical properties, and this polymorphism has been associated with the susceptibility to and outcome of several human pathologies [11][12][13] . The most firmly established biological function of Hp is its strong binding to free hemoglobin (Hb) 10,14 .…”

Section: Introductionmentioning

confidence: 99%

Genótipos de haptoglobina e hipertensão refratária em pacientes com diabete melito tipo 2

Wobeto¹,

Pinho²,

Souza³

et al. 2011

Arq. Bras. Cardiol.

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Section: Introductionmentioning

confidence: 99%

Genótipos de haptoglobina e hipertensão refratária em pacientes com diabete melito tipo 2

Wobeto¹,

Pinho²,

Souza³

et al. 2011

Arq. Bras. Cardiol.

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“…HP has a wide variety of functions in biological systems, such as binding to free hemoglobin to prevent iron loss and kidney damage during hemolysis, protection against oxidative damage/toxic radical, inhibition of nitric oxide, angiogenesis, and others [12]. To date, several studies have reported that HP level in peripheral blood is elevated in cancer patients including gastric, liver, non-small cell lung, and pancreatic cancer compared to benign tumors or normal subjects [23][24][25][26].…”

Section: Discussionmentioning

confidence: 99%

“…Among the promoter polymorphisms listed in Table 2, Fisher's exact test revealed that only the HP promoter polymorphism −55A>G (dbSNP ID: rs5472) bears a statistically significant relationship to clinical outcome in CRPC patients receiving PPV (P < 0.001). rs5472 is predominant in all populations [12,21]. There are three genotypes arising from the −55A>G locus (A/A, A/G, and G/G).…”

Section: Promoter Polymorphism Of the Mpo Hp And Elanementioning

confidence: 99%

“…In humans, the HP locus is polymorphic, with two codominant alleles referred to as HP1 and HP2 that yield three distinct phenotypes (HP1-1, HP2-1, and HP2-2). There are many reports of the association of HP phenotype with various diseases such as cancer, cardiovascular disease, infection disease, and neurological disease [12], and with the immune response to hepatitis B vaccination and typhoid vaccination [13,14], whereas there is little information about clinical importance and relevance of HP promoter polymorphism. In this study, we analyzed promoter sequence of HP in vaccinated CRPC patients and identified five promoter polymorphisms.…”

Section: Introductionmentioning

confidence: 99%

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Haptoglobin promoter polymorphism rs5472 as a prognostic biomarker for peptide vaccine efficacy in castration-resistant prostate cancer patients

Araki

Pang

Komatsu

et al. 2015

Cancer Immunol Immunother

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Personalized peptide vaccination (PPV) is an attractive approach to cancer immunotherapy with strong immune-boosting effects conferring significant clinical benefit. However, as with most therapeutic agents, there is a difference in clinical efficacy among patients receiving PPV. Therefore, a useful biomarker is urgently needed for prognosticating clinical outcomes to preselect patients who would benefit the most from PPV. In this retrospective study, to detect a molecular prognosticator of clinical outcomes for PPV, we analyzed whole-genome gene expression profiles of peripheral blood mononuclear cells (PBMCs) in castration-resistant prostate cancer (CRPC) patients before administration of PPV. Cox regression analysis revealed that mRNA expression of myeloperoxidase, haptoglobin, and neutrophil elastase was significantly associated with overall survival (OS) among vaccinated CRPC patients (adjusted P < 0.01). By promoter sequence analysis of these three genes, we found that rs5472 of haptoglobin (HP), an acute-phase plasma glycoprotein, was strongly correlated to OS of vaccinated CRPC patients (P = 0.0047, hazard ratio 0.47; 95 % confidence interval 0.28-0.80). Furthermore, both HP mRNA expression in PBMCs and protein level in plasma of CRPC patients before administration of PPV exhibited rs5472 dependence (P < 0.001 for mRNA expression and P < 0.05 for protein level). Our findings suggest that rs5472 may play an important role in the immune response to PPV via regulation of HP. Thus, we concluded that rs5472 is a potential prognostic biomarker for PPV.

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“…The structural and functional differences between Hp phenotypes in humans have important biological and clinical consequences. Hp polymorphism has been reported to associate with the prevalence and clinical evolution of several infectious diseases and autoimmune disorders [11]. In this study, it is aimed to investigate the age-related changes in concentrations of some non-enzymatic antioxidants, haptoglobin phenotypes and serum electrophoretic profiles in rats.…”

Section: Introductionmentioning

confidence: 99%

Age-related changes in haptoglobin phenotypes, some non-enzymatic antioxidants and electrophoretic profiles of serum proteins in rats

Çiftçi

Yarım²,

Çenesiz³

et al. 2012

Turk J Bioch

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Aim: Determination of age-related changes in levels of some non-enzymatic antioxidants such as serum haptoglobin, haemoglobin and albumin, serum haptoglobin phenotype and serum protein profile was aimed with this study. Methods and results: Fifty Sprague-Dawley male rats were divided equally into five groups as 1 (one-month old), 2 (six-months old), 3 (twelve-months old), 4 (eighteen-months old) and 5 (twenty-four-months old). The serum protein concentrations were measured by autoanalyzer. A decrease was determined in the concentrations of the total protein and albumin related to age. However, no clear decrease in the serum globulin concentrations occurred. Serum haptoglobin concentrations were measured by ELISA and an increase was detected with age. Serum haemoglobin concentrations were increased up to 3 months old, but decreased from 3 to 24 months old of age. The electrophoretic profiles of serum total protein were determined by native-PAGE. No differences were observed in total serum profiles between age groups. To determine serum haptoglobin profiles, western blot was performed and haptoglobin patterns were designated as "aa" (single band) or "ab" (two bands) patterns. The "ab" pattern was more frequently observed in older rats. Also, 15 protein bands ranged between 19 to 244 kDa, were detected by SDS-PAGE. After SDS-PAGE, western blot were performed and three haptoglobin bands (10, 37 and 47 kDa) were detected. Conclusion:The age-related changes in total serum protein, albumin, haemoglobin and haptoglobin concentrations as well as the prevalent haptoglobin phenotypes may be considered as indicators in some age-related diseases.

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Polymorphism of human haptoglobin and its clinical importance

Cited by 56 publications

References 169 publications

Genótipos de haptoglobina e hipertensão refratária em pacientes com diabete melito tipo 2

Genótipos de haptoglobina e hipertensão refratária em pacientes com diabete melito tipo 2

Haptoglobin promoter polymorphism rs5472 as a prognostic biomarker for peptide vaccine efficacy in castration-resistant prostate cancer patients

Age-related changes in haptoglobin phenotypes, some non-enzymatic antioxidants and electrophoretic profiles of serum proteins in rats

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