TY - JOUR
T1 - A Genome-Wide Association Study Identifies rs2000999 as a Strong Genetic Determinant of Circulating Haptoglobin Levels
AU - Froguel, Philippe
AU - Ndiaye, Ndeye Coumba
AU - Bonnefond, Amélie
AU - Bouatia-Naji, Nabila
AU - Dechaume, Aurélie
AU - Siest, Gérard
AU - Herbeth, Bernard
AU - Falchi, Mario
AU - Bottolo, Leonardo
AU - Guéant-Rodriguez, Rosa-Maria
AU - Lecoeur, Cécile
AU - Langlois, Michel R.
AU - Labrune, Yann
AU - Ruokonen, Aimo
AU - El Shamieh, Said
AU - Stathopoulou, Maria G.
AU - Morandi, Anita
AU - Maffeis, Claudio
AU - Meyre, David
AU - Delanghe, Joris R.
AU - Jacobson, Peter
AU - Sjöström, Lars
AU - Carlsson, Lena M. S.
AU - Walley, Andrew
AU - Elliott, Paul
AU - Jarvelin, Marjo-Riita
AU - Dedoussis, George V.
AU - Visvikis-Siest, Sophie
PY - 2012/3/5
Y1 - 2012/3/5
N2 - 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 × 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 (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.
AB - 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 × 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 (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.
KW - Adult
KW - Cardiovascular Diseases
KW - Child
KW - Female
KW - Genome-Wide Association Study
KW - Genotype
KW - Haptoglobins
KW - Humans
KW - Male
KW - Polymorphism, Single Nucleotide
KW - Risk Factors
U2 - 10.1371/journal.pone.0032327
DO - 10.1371/journal.pone.0032327
M3 - Article
C2 - 22403646
SN - 1932-6203
VL - 7
SP - e32327
JO - PLoS ONE
JF - PLoS ONE
IS - 3
ER -