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

Philippe Froguel, Ndeye Coumba Ndiaye, Amélie Bonnefond, Nabila Bouatia-Naji, Aurélie Dechaume, Gérard Siest, Bernard Herbeth, Mario Falchi, Leonardo Bottolo, Rosa-Maria Guéant-Rodriguez, et al. (2012) PLOS ONE. 7(3).
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
PEDIGREE ANALYSIS, CARDIOVASCULAR-DISEASES, ADIPOSE-TISSUE, RISK-FACTORS, POLYMORPHISM, HEMOGLOBIN, PHENOTYPE, INFLAMMATION, CHRONIC HEPATITIS-C, PLASMA-GLUCOSE LEVELS
journal title
PLOS ONE
PLoS One
volume
7
issue
3
article number
e32327
pages
9 pages
Web of Science type
Article
Web of Science id
000303017700043
JCR category
MULTIDISCIPLINARY SCIENCES
JCR impact factor
3.73 (2012)
JCR rank
7/56 (2012)
JCR quartile
1 (2012)
ISSN
1932-6203
DOI
10.1371/journal.pone.0032327
language
English
UGent publication?
yes
classification
A1
copyright statement
I have retained and own the full copyright for this publication
id
3162772
handle
http://hdl.handle.net/1854/LU-3162772
date created
2013-03-11 15:28:26
date last changed
2016-12-21 15:42:34
@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},
}

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.