| Unraveling the directional link between adiposity and inflammation: a bidirectional Mendelian randomization approach. | |
| | |
MedLine Citation:
|
PMID: 19906786 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
CONTEXT: Associations between adiposity and circulating inflammation markers are assumed to be causal, although the direction of the relationship has not been proven. OBJECTIVE: The aim of the study was to explore the causal direction of the relationship between adiposity and inflammation using a bidirectional Mendelian randomization approach. METHODS: In the PROSPER study of 5804 elderly patients, we related C-reactive protein (CRP) single nucleotide polymorphisms (SNPs) (rs1800947 and rs1205) and adiposity SNPs (FTO and MC4R) to body mass index (BMI) as well as circulating levels of CRP and leptin. We gave each individual two allele scores ranging from zero to 4, counting each pair of alleles related to CRP levels or BMI. RESULTS: With increasing CRP allele score, there was a stepwise decrease in CRP levels (P for trend < 0.0001) and a 1.98 mg/liter difference between extremes of the allele score distribution, but there was no associated change in BMI or leptin levels (P >or= 0.89). By contrast, adiposity allele score was associated with 1) an increase in BMI (1.2 kg/m(2) difference between extremes; P for trend 0.002); 2) an increase in circulating leptin (5.77 ng/ml difference between extremes; P for trend 0.0027); and 3) increased CRP levels (1.24 mg/liter difference between extremes; P for trend 0.002). CONCLUSIONS: Greater adiposity conferred by FTO and MC4R SNPs led to higher CRP levels, with no evidence for any reverse pathway. Future studies should extend our findings to other circulating inflammatory parameters. This study illustrates the potential power of Mendelian randomization to dissect directions of causality between intercorrelated metabolic factors. |
| | |
Authors:
|
Paul Welsh; Eliana Polisecki; Michele Robertson; Sabine Jahn; Brendan M Buckley; Anton J M de Craen; Ian Ford; J Wouter Jukema; Peter W Macfarlane; Chris J Packard; David J Stott; Rudi G J Westendorp; James Shepherd; Aroon D Hingorani; George Davey Smith; Ernst Schaefer; Naveed Sattar |
Related Documents
:
|
15870396 - Linkage and association analyses of the ucp3 gene with obesity phenotypes in caucasian ... 11096266 - C677t methylenetetrahydrofolate reductase polymorphism is not a risk factor for pre-ecl... 12807506 - The relation between two polymorphisms in the glucocorticoid receptor gene and body mas... 11151766 - Linkage and association studies between the proopiomelanocortin (pomc) gene and obesity... 23193976 - Latitudinal clines in alternative life histories in a geometrid moth. 19419586 - Association of a single nucleotide polymorphism in titin gene with marbling in japanese... |
Publication Detail:
|
Type: Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2009-11-11 |
Journal Detail:
|
Title: The Journal of clinical endocrinology and metabolism Volume: 95 ISSN: 1945-7197 ISO Abbreviation: J. Clin. Endocrinol. Metab. Publication Date: 2010 Jan |
Date Detail:
|
Created Date: 2010-01-08 Completed Date: 2010-02-01 Revised Date: 2013-03-11 |
Medline Journal Info:
|
Nlm Unique ID: 0375362 Medline TA: J Clin Endocrinol Metab Country: United States |
Other Details:
|
Languages: eng Pagination: 93-9 Citation Subset: AIM; IM |
Affiliation:
|
Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adiposity
/
genetics* Aged Aged, 80 and over Biological Markers / blood C-Reactive Protein / genetics Female Genetic Linkage* Genetic Markers / physiology Genotype Humans Inflammation / blood, genetics* Male Mendelian Randomization Analysis / methods* Polymorphism, Single Nucleotide Proteins / genetics Receptor, Melanocortin, Type 4 / genetics |
| Grant Support | |
ID/Acronym/Agency:
|
R01 HL74753/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Biological Markers; 0/FTO protein, human; 0/Genetic Markers; 0/MC4R protein, human; 0/Proteins; 0/Receptor, Melanocortin, Type 4; 9007-41-4/C-Reactive Protein |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Serum Thyroid-Stimulating Hormone Concentration and Morbidity from Cardiovascular Disease and Fractu...
Next Document: Long-Term Safety of Recombinant Human Growth Hormone in Children.