A Genome-Wide Association Study Identifies rs2000999 as a Strong Genetic Determinant of Circulating Haptoglobin LevelsReport as inadecuate




A Genome-Wide Association Study Identifies rs2000999 as a Strong Genetic Determinant of Circulating Haptoglobin Levels - Download this document for free, or read online. Document in PDF available to download.

Haptoglobin is an acute phase inflammatory marker. Its main function is to bind hemoglobin released from erythrocytes to aid its elimination, and thereby haptoglobin prevents the generation of reactive oxygen species in the blood. Haptoglobin levels have been repeatedly associated with a variety of inflammation-linked infectious and non-infectious diseases, including malaria, tuberculosis, human immunodeficiency virus, hepatitis C, diabetes, carotid atherosclerosis, and acute myocardial infarction. However, a comprehensive genetic assessment of the inter-individual variability of circulating haptoglobin levels has not been conducted so far.We used a genome-wide association study initially conducted in 631 French children followed by a replication in three additional European sample sets and we identified a common single nucleotide polymorphism SNP, rs2000999 located in the Haptoglobin gene HP as a strong genetic predictor of circulating Haptoglobin levels Poverall = 8.1×10−59, explaining 45.4% of its genetic variability 11.8% of Hp global variance. The functional relevance of rs2000999 was further demonstrated by its specific association with HP mRNA levels β = 0.23±0.08, P = 0.007. Finally, SNP rs2000999 was associated with decreased total and low-density lipoprotein cholesterol in 8,789 European children Ptotal cholesterol = 0.002 and PLDL = 0.0008.Given the central position of haptoglobin in many inflammation-related metabolic pathways, the relevance of rs2000999 genotyping when evaluating haptoglobin concentration should be further investigated in order to improve its diagnostic-therapeutic and-or prevention impact.



Author: Philippe Froguel , Ndeye Coumba Ndiaye , Amélie Bonnefond, Nabila Bouatia-Naji, Aurélie Dechaume, Gérard Siest, Bernard Herbet

Source: http://plos.srce.hr/



DOWNLOAD PDF




Related documents