Haptoglobin Duplicon, Hemoglobin, and Vitamin C: Analyses in the British Women’s Heart and Health Study and Caerphilly Prospective Study

Background. Haptoglobin acts as an antioxidant by limiting peroxidative tissue damage by free hemoglobin. The haptoglobin gene allele Hp2 comprises a 1.7 kb partial duplication. Relative to allele Hp1, Hp2 carriers form protein multimers, suboptimal for hemoglobin scavenging.Objective. To examine the association of haptoglobin genotype with a range of phenotypes, with emphasis on vitamin C and hemoglobin levels.Methods. We applied a quantitative PCR assay for the duplication junction to two population cohorts including 2747 British women and 1198 British men. We examined the association of haptoglobin duplicon copy number with hemoglobin and vitamin C and used the copy number to complete a phenome scan.Results.Hemoglobin concentrations were greater in those with Hp2,2 genotype, in women only (Hp1,1 13.45 g/dL, Hp1,2 13.49 g/dL, Hp2,2 13.61 g/dL;P=0.002), though statistically there was no evidence of a difference between the sexes (zvalue = 1.2,P=0.24). Haptoglobin genotype was not associated with vitamin C or any other phenotype in either cohort.Conclusions. Our results do not support association of haptoglobin genotype with vitamin C or with other phenotypes measured in two population cohorts. The apparent association between haptoglobin genotype and hemoglobin in the women’s cohort merits further investigation.

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Quantification of MYCN, DDX1, and NAG Gene Copy Number in Neuroblastoma Using a Real-Time Quantitative PCR Assay

Modern Pathology ◽

10.1038/modpathol.3880508 ◽

2002 ◽

Vol 15 (2) ◽

pp. 159-166 ◽

Cited By ~ 136

Author(s):

Katleen De Preter ◽

Frank Speleman ◽

Valérie Combaret ◽

John Lunec ◽

Geneviève Laureys ◽

...

Keyword(s):

Real Time ◽

Quantitative Pcr ◽

Copy Number ◽

Gene Copy Number ◽

Gene Copy ◽

Pcr Assay ◽

Real Time Quantitative Pcr ◽

Quantitative Pcr Assay

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Haptoglobin Gene Polymorphism among Sickle Cell Patients in West Cameroon: Hematological and Clinical Implications

Advances in Hematology ◽

10.1155/2021/6939413 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Christian Bernard Kengne Fotsing ◽

Constant Anatole Pieme ◽

Prosper Cabral Biapa Nya ◽

Jean Paul Chedjou ◽

Samuel Ashusong ◽

...

Keyword(s):

Disease Severity ◽

Sickle Cell ◽

Hematological Parameters ◽

Clinical Manifestations ◽

The Body ◽

Free Hemoglobin ◽

Significant Difference ◽

Haptoglobin Genotype ◽

The Impact ◽

Haptoglobin Gene

Haptoglobin is a protein involved in protecting the body from the harmful effects of free hemoglobin. The haptoglobin gene exhibits a polymorphism, and the different genotypes do not have the same capacity to combat the free hemoglobin effects. The present study aimed at determining the polymorphic distribution of haptoglobin in sickle cell patients (SCPs) from West Cameroon and their impact on the hematological parameters, as well as clinical manifestations of the disease severity. Haptoglobin genotype of 102 SCPs (SS) and 115 healthy individuals (60 AA and 55 AS) was determined by allele-specific polymerase chain reaction, and the complete blood count was determined using the AutoAnalyser. Results showed that the genotype Hp2-2 was significantly ( p < 0.05) represented in SS patients (54%) than in controls AA and AS (27% and 29%, respectively), while Hp2-1 was mostly found ( p < 0.05) in AS (42%) and AA (38%), against 15% in SS. The allelic distribution in SS patients was Hp2: 0.613, Hp1S: 0.304, and Hp1F: 0.084. In AA and AS controls, the proportions of the Hp1 and Hp2 alleles were similar (around 0.5 each), with 0.282 for Hp1S and 0.218 for Hp1F in AS and 0.283 for Hp1S and 0.258 for Hp1F in AA. The distribution of the haptoglobin genotypes did not reveal any significant difference across hematological parameters and clinical manifestations of disease severity in SCP and controls. SCP with Hp1S-1F genotype presented the highest level of hemoglobin. Although Hp2-2 was more frequent in SS patients, it appeared not to be related to the hematological parameters and to the disease’s severity. Further investigations are necessary to explore the impact of Hp polymorphism such as antioxidant, lipid profile, and functionality of some tissues in SCP in Cameroon.

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Development of copy number assays for detection and surveillance of piperaquine resistance associated plasmepsin 2/3 copy number variation in Plasmodium falciparum

10.1101/655209 ◽

2019 ◽

Author(s):

Christopher G Jacob ◽

Megan R Ansbro ◽

Roberto Amato ◽

Mihir Kekre ◽

Ranitha Vongpromek ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Copy Number Variation ◽

Southeast Asia ◽

Quantitative Pcr ◽

Copy Number ◽

Dried Blood Spots ◽

Pcr Assay ◽

Number Variation ◽

Preah Vihear ◽

Quantitative Pcr Assay

AbstractLong regarded as an epicenter of drug-resistant malaria, Southeast Asia continues to provide new challenges to the control of Plasmodium falciparum malaria. Recently, resistance to the artemisinin combination therapy partner drug piperaquine has been observed in multiple locations across Southeast Asia. Genetic studies have identified a single nucleotide polymorphism as well as a copy number variation molecular marker that associate with clinical and in vitro resistance. The copy number polymorphism is a duplication of a region containing members of the plasmepsin multi-gene family of proteases. To accurately and quickly determine the presence of copy number variation in the plasmepsin 2/3 duplication in field isolates, we developed a quantitative PCR assay using TaqMan probes. We validated copy number estimates using a separate SYBR green-based quantitative PCR assay as well as a novel breakpoint assay to detect the hybrid gene product. Field samples from 2012 – 2015 across 3 sites in Cambodia were tested using DNA extracted from dried blood spots and whole blood to monitor the extent of plasmepsin 2/3 gene duplications, as well as pfmdr1. We found high concordance across all methods of copy number detection. For samples derived from dried blood spots we found a greater than 80% success rate in each assay, with more recent samples performing better. We found evidence of extensive plasmepsin 2/3 copy number amplifications in Pursat (94%, 2015) and Preah Vihear (87%, 2014), and lower levels in Ratanakiri (16%, 2014) in eastern Cambodia. We also see evidence of a shift from two copies of plasmepsin 2/3 in Pursat 2013 to three copies in 2014-15 (25% to 64%). Pfmdr1 duplications are absent from all samples in 2014 from Preah Vihear and Ratanakiri and 2015 from Pursat. This study shows increasing levels of plasmepsin 2/3 gene amplifications across Cambodia from 2012 – 2015 and a complete reversion of pfmdr1 mutant parasites in all study locations. The multiplex TaqMan assay is a robust tool for monitoring both plasmepsin and pfmdr1 copy number variations in field isolates, and the SYBR-green and breakpoint assays are useful for monitoring plasmepsin 2/3 duplications.

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