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Diabetes Publish Ahead of Print published online ahead of print April 21, 2008
DOI: 10.2337/db08-0270
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Original Research

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 Hakonarson2,,3, and Constantin Polychronakos1

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

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 ({alpha}=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.

Correspondence: hakonarson{at}chop.edu

Correspondence: constantin.polychronakos{at}mcgill.ca

Key Words: Etiology • Genetic susceptibility • Type 1 diabetes • Type 2 diabetes


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