No evidence for a causal link between uric acid and type 2 diabetes: a Mendelian randomisation approach.

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Serval ID
serval:BIB_6217D466F4BF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
No evidence for a causal link between uric acid and type 2 diabetes: a Mendelian randomisation approach.
Journal
Diabetologia
Author(s)
Pfister Roman, Barnes Daniel, Luben Robert N., Forouhi Nita G., Bochud Murielle, Khaw Kay-Tee, Wareham Nicholas J., Langenberg Claudia
ISSN
1432-0428 (Electronic)
ISSN-L
0012-186X
Publication state
Published
Issued date
2011
Peer-reviewed
Oui
Volume
54
Number
10
Pages
2561-2569
Language
english
Abstract
AIMS/HYPOTHESIS: Epidemiological and experimental evidence suggests that uric acid has a role in the aetiology of type 2 diabetes. Using a Mendelian randomisation approach, we investigated whether there is evidence for a causal role of serum uric acid for development of type 2 diabetes.
METHODS: We examined the associations of serum-uric-acid-raising alleles of eight common variants recently identified in genome-wide association studies and summarised this in a genetic score with type 2 diabetes in case-control studies including 7,504 diabetes patients and 8,560 non-diabetic controls. We compared the observed effect size to that expected based on: (1) the association between the genetic score and uric acid levels in non-diabetic controls; and (2) the meta-analysed uric acid level to diabetes association.
RESULTS: The genetic score showed a linear association with uric acid levels, with a difference of 12.2 μmol/l (95% CI 9.3, 15.1) by score tertile. No significant associations were observed between the genetic score and potential confounders. No association was observed between the genetic score and type 2 diabetes with an OR of 0.99 (95% CI 0.94, 1.04) per score tertile, significantly different (p = 0.046) from that expected (1.04 [95% CI 1.03, 1.05]) based on the observed uric acid difference by score tertile and the uric acid to diabetes association of 1.21 (95% CI 1.14, 1.29) per 60 μmol/l.
CONCLUSIONS/INTERPRETATION: Our results do not support a causal role of serum uric acid for the development of type 2 diabetes and limit the expectation that uric-acid-lowering drugs will be effective in the prevention of type 2 diabetes.
Keywords
Adult, Aged, Alleles, Case-Control Studies, Diabetes Mellitus, Type 2/blood, Diabetes Mellitus, Type 2/epidemiology, Female, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Uric Acid/blood
Pubmed
Web of science
Open Access
Yes
Create date
08/11/2011 15:50
Last modification date
20/08/2019 14:19
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