Association analysis of the type 2 diabetes loci in type 1 diabetes
- Hui-Qi Qu1,
- Struan F.A. Grant2,,3,
- Jonathan P. Bradfield2,
- Cecilia Kim2,
- Edward Frackelton2,
- Hakon Hakonarson (hakonarson{at}chop.edu)2,,3 and
- Constantin Polychronakos (constantin.polychronakos{at}mcgill.ca)1
- 1Departments of Pediatrics and Human Genetics, McGill University, Montreal H4H 2P4, Québec, Canada
- 2Center for Applied Genomics, and
- 3Department of Pediatrics and Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 29205, USA
Abstract
Objective: To search for a possible association of type 1 diabetes with ten validated type 2 diabetes (type 2 diabetes) loci, i.e. PPARG, KCNJ11, WFS1, HNF1B, IDE/HHEX, SLC30A8, CDKAL1, CDKN2A/B, IGF2BP2, and FTO/RPGRIP1L.
Research Design and Methods: Two European population samples were studied: one case-control cohort of 514 type 1 diabetes cases and 2,027 controls, and one family cohort of 483 complete type 1 diabetes case-parent trios (total 997 affected). Thirteen tag SNPs from the ten type 2 diabetes loci were analyzed for type 1 diabetes association.
Results: No association of type 1 diabetes was found with any of the ten type 2 diabetes loci and no age-of-onset effect was detected. By combined analysis using the Wellcome Trust Case-Control Consortium type 1 diabetes data, SNP rs1412829 in the CDKN2A/B locus show bordering significance (P=0.039), OR (95% CI)=0.929 (0.867, 0.995), which did not reach the statistical significance threshold adjusted for 13 tests (α=0.00385).
Conclusions: This study suggests that the type 2 diabetes loci do not play any obvious role in type 1 diabetes genetic susceptibility. The distinct molecular mechanisms of the two diseases highlighted the importance of differentiation diagnosis and different treatment principles.
Footnotes
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- Received February 24, 2008.
- Accepted April 15, 2008.
- Copyright © American Diabetes Association
