Back to Search
Start Over
A Genome-Wide Association Study Identifies rs2000999 as a Strong Genetic Determinant of Circulating Haptoglobin Levels
- Source :
- PLoS ONE, Froguel, P, Ndiaye, N C, Bonnefond, A, Bouatia-Naji, N, Dechaume, A, Siest, G, Herbeth, B, Falchi, M, Bottolo, L, Guéant-Rodriguez, R-M, Lecoeur, C, Langlois, M R, Labrune, Y, Ruokonen, A, El Shamieh, S, Stathopoulou, M G, Morandi, A, Maffeis, C, Meyre, D, Delanghe, J R, Jacobson, P, Sjöström, L, Carlsson, L M S, Walley, A, Elliott, P, Jarvelin, M-R, Dedoussis, G V & Visvikis-Siest, S 2012, ' A Genome-Wide Association Study Identifies rs2000999 as a Strong Genetic Determinant of Circulating Haptoglobin Levels ', PLoS ONE, vol. 7, no. 3, pp. e32327 . https://doi.org/10.1371/journal.pone.0032327, PLOS ONE, PLoS ONE; Vol 7, PLoS ONE, Vol 7, Iss 3, p e32327 (2012)
- Publication Year :
- 2012
- Publisher :
- Public Library of Science, 2012.
-
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 × 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.
- Subjects :
- Male
PEDIGREE ANALYSIS
Epidemiology
lcsh:Medicine
Genome-wide association study
030204 cardiovascular system & hematology
PHENOTYPE
Pediatrics
genome-wide
0302 clinical medicine
Risk Factors
Genotype
lcsh:Science
Child
HEMOGLOBIN
0303 health sciences
Multidisciplinary
Haptoglobin
Genomics
haptoglobin
3. Good health
ADIPOSE-TISSUE
Infectious Diseases
Cardiovascular Diseases
Science & Technology - Other Topics
Medicine
Female
Public Health
CHRONIC HEPATITIS-C
Research Article
Adult
children
General Science & Technology
Immunology
Single-nucleotide polymorphism
Biology
Polymorphism, Single Nucleotide
03 medical and health sciences
INFLAMMATION
Genome Analysis Tools
Diagnostic Medicine
Diabetes mellitus
MD Multidisciplinary
medicine
Genetics
SNP
Humans
Genetic variability
Genotyping
030304 developmental biology
Clinical Genetics
Science & Technology
Population Biology
Haptoglobins
MULTIDISCIPLINARY SCIENCES
lcsh:R
Immunity
Biology and Life Sciences
Computational Biology
Human Genetics
medicine.disease
POLYMORPHISM
PLASMA-GLUCOSE LEVELS
CARDIOVASCULAR-DISEASES
RISK-FACTORS
biology.protein
lcsh:Q
Clinical Immunology
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 7
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....f8ac4b43ff17b7d6d63e9b62850ec3d7