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01-12-2008 | Article

Gene variants influencing measures of inflammation or predisposing to autoimmune and inflammatory diseases are not associated with the risk of type 2 diabetes

Authors: S. Rafiq, D. Melzer, M. N. Weedon, H. Lango, R. Saxena, L. J. Scott, C. N. A. Palmer, A. D. Morris, M. I. McCarthy, L. Ferrucci, A. T. Hattersley, E. Zeggini, T. M. Frayling, the DIAGRAM Consortium

Published in: Diabetologia | Issue 12/2008

Abstract

Aims/hypothesis

There are strong associations between measures of inflammation and type 2 diabetes, but the causal directions of these associations are not known. We tested the hypothesis that common gene variants known to alter circulating levels of inflammatory proteins, or known to alter autoimmune-related disease risk, influence type 2 diabetes risk.

Methods

We selected 46 variants: (1) eight variants known to alter circulating levels of inflammatory proteins, including those in the IL18, IL1RN, IL6R, MIF, PAI1 (also known as SERPINE1) and CRP genes; and (2) 38 variants known to predispose to autoimmune diseases, including type 1 diabetes. We tested the associations of these variants with type 2 diabetes using a meta-analysis of 4,107 cases and 5,187 controls from the Wellcome Trust Case Control Consortium, the Diabetes Genetics Initiative, and the Finland–United States Investigation of NIDDM studies. We followed up associated variants (p < 0.01) in a further set of 3,125 cases and 3,596 controls from the UK.

Results

We found no evidence that inflammatory or autoimmune disease variants are associated with type 2 diabetes (at p ≤ 0.01). The OR observed between the variant altering IL-18 levels, rs2250417, and type 2 diabetes (OR 1.00 [95% CI 0.99–1.03]), is much lower than that expected given (1) the effect of the variant on IL-18 levels (0.28 SDs per allele); and (2) estimates, based on other studies, of the correlation between IL-18 levels and type 2 diabetes risk (approximate OR 1.15 [95% CI 1.09–1.21] per 0.28 SD increase in IL-18 levels).

Conclusions/interpretation

Our study provided no evidence that variants known to alter measures of inflammation, autoimmune or inflammatory disease risk, including type 1 diabetes, alter type 2 diabetes risk.

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Title: Gene variants influencing measures of inflammation or predisposing to autoimmune and inflammatory diseases are not associated with the risk of type 2 diabetes
Authors: S. Rafiq
D. Melzer
M. N. Weedon
H. Lango
R. Saxena
L. J. Scott
C. N. A. Palmer
A. D. Morris
M. I. McCarthy
L. Ferrucci
A. T. Hattersley
E. Zeggini
T. M. Frayling
the DIAGRAM Consortium
Publication date: 01-12-2008
Publisher: Springer-Verlag
Published in: Diabetologia / Issue 12/2008
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-008-1160-3

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Conclusions/interpretation

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