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Diabetologia
Published in: Diabetologia 10/2009

Open Access 01-10-2009 | Article

No association of multiple type 2 diabetes loci with type 1 diabetes

Authors: S. M. Raj, J. M. M. Howson, N. M. Walker, J. D. Cooper, D. J. Smyth, S. F. Field, H. E. Stevens, J. A. Todd

Published in: Diabetologia | Issue 10/2009

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Abstract

Aims/hypothesis

We used recently confirmed type 2 diabetes gene regions to investigate the genetic relationship between type 1 and type 2 diabetes, in an average of 7,606 type 1 diabetic individuals and 8,218 controls, providing >80% power to detect effects as small as an OR of 1.11 at a false-positive rate of 0.003.

Methods

The single nucleotide polymorphisms (SNPs) with the most convincing evidence of association in 12 type 2 diabetes-associated gene regions, PPARG, CDKAL1, HNF1B, WFS1, SLC30A8, CDKN2A–CDKN2B, IGF2BP2, KCNJ11, TCF7L2, FTO, HHEX–IDE and THADA, were analysed in type 1 diabetes cases and controls. PPARG and HHEX–IDE were additionally tested for association in 3,851 type 1 diabetes families. Tests for interaction with HLA class II genotypes, autoantibody status, sex, and age-at-diagnosis of type 1 diabetes were performed with all 12 gene regions.

Results

Only PPARG and HHEX–IDE showed any evidence of association with type 1 diabetes cases and controls (p = 0.004 and p = 0.003, respectively; p > 0.05 for other SNPs). The potential association of PPARG was supported by family analyses (p = 0.003; p combined = 1.0 × 10−4). No SNPs showed evidence of interaction with any covariate (p > 0.05).

Conclusions/interpretation

We found no convincing genetic link between type 1 and type 2 diabetes. An association of PPARG (rs1801282/Pro12Ala) could be consistent with its known function in inflammation. Hence, our results reinforce evidence suggesting that type 1 diabetes is a disease of the immune system, rather than being due to inherited defects in beta cell function or regeneration or insulin resistance.
Appendix
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Metadata
Title
No association of multiple type 2 diabetes loci with type 1 diabetes
Authors
S. M. Raj
J. M. M. Howson
N. M. Walker
J. D. Cooper
D. J. Smyth
S. F. Field
H. E. Stevens
J. A. Todd
Publication date
01-10-2009
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 10/2009
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-009-1391-y

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