Advanced search
1 file | 304.48 KB

A genome-wide association study identifies rs2000999 as a strong genetic determinant of circulating haptoglobin levels

(2012) PLOS ONE. 7(3).
Author
Organization
Abstract
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 (P-overall = 8.1 x 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 (beta = 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 (P-total cholesterol = 0.002 and P-LDL = 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.
Keywords
PEDIGREE ANALYSIS, CARDIOVASCULAR-DISEASES, ADIPOSE-TISSUE, RISK-FACTORS, POLYMORPHISM, HEMOGLOBIN, PHENOTYPE, INFLAMMATION, CHRONIC HEPATITIS-C, PLASMA-GLUCOSE LEVELS

Downloads

  • A Genome-Wide Association Study Identifies rs2000999 as a Strong Genetic Determinant of Circulating Haptoglobin Levels.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 304.48 KB

Citation

Please use this url to cite or link to this publication:

Chicago
Froguel, Philippe, Ndeye Coumba Ndiaye, Amélie Bonnefond, Nabila Bouatia-Naji, Aurélie Dechaume, Gérard Siest, Bernard Herbeth, et al. 2012. “A Genome-wide Association Study Identifies Rs2000999 as a Strong Genetic Determinant of Circulating Haptoglobin Levels.” Plos One 7 (3).
APA
Froguel, P., Ndiaye, N. C., Bonnefond, A., Bouatia-Naji, N., Dechaume, A., Siest, G., Herbeth, B., et al. (2012). A genome-wide association study identifies rs2000999 as a strong genetic determinant of circulating haptoglobin levels. PLOS ONE, 7(3).
Vancouver
1.
Froguel P, Ndiaye NC, Bonnefond A, Bouatia-Naji N, Dechaume A, Siest G, et al. A genome-wide association study identifies rs2000999 as a strong genetic determinant of circulating haptoglobin levels. PLOS ONE. 2012;7(3).
MLA
Froguel, Philippe, Ndeye Coumba Ndiaye, Amélie Bonnefond, et al. “A Genome-wide Association Study Identifies Rs2000999 as a Strong Genetic Determinant of Circulating Haptoglobin Levels.” PLOS ONE 7.3 (2012): n. pag. Print.
@article{3162772,
  abstract     = {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 (P-overall = 8.1 x 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 (beta = 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 (P-total cholesterol = 0.002 and P-LDL = 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.},
  articleno    = {e32327},
  author       = {Froguel, Philippe and Ndiaye, Ndeye Coumba and Bonnefond, Am{\'e}lie and Bouatia-Naji, Nabila and Dechaume, Aur{\'e}lie and Siest, G{\'e}rard and Herbeth, Bernard and Falchi, Mario and Bottolo, Leonardo and Gu{\'e}ant-Rodriguez, Rosa-Maria and Lecoeur, C{\'e}cile and Langlois, Michel and Labrune, Yann and Ruokonen, Aimo and El Shamieh, Said and Stathopoulou, Maria G and Morandi, Anita and Maffeis, Claudio and Meyre, David and Delanghe, Joris and Jacobson, Peter and Sj{\"o}str{\"o}m, Lars and Carlsson, Lena MS and Walley, Andrew and Elliott, Paul and Jarvelin, Marjo-Riita and Dedoussis, George V and Visvikis-Siest, Sophie},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keyword      = {PEDIGREE ANALYSIS,CARDIOVASCULAR-DISEASES,ADIPOSE-TISSUE,RISK-FACTORS,POLYMORPHISM,HEMOGLOBIN,PHENOTYPE,INFLAMMATION,CHRONIC HEPATITIS-C,PLASMA-GLUCOSE LEVELS},
  language     = {eng},
  number       = {3},
  pages        = {9},
  title        = {A genome-wide association study identifies rs2000999 as a strong genetic determinant of circulating haptoglobin levels},
  url          = {http://dx.doi.org/10.1371/journal.pone.0032327},
  volume       = {7},
  year         = {2012},
}

Altmetric
View in Altmetric
Web of Science
Times cited: