Association analysis of type 2 diabetes loci in type 1 diabetes

OBJECTIVE-To search for a possible association of type I diabetes with 10 validated type 2 diabetes loci, i.e., PPARG, KCNJ11, WFS1, HNF1B, IDE/HHEX, SLC3OA8, CDKAL1, CDKN2A/B, IGF2BP2, and FTO/RPGRIP1L. RESEARCH DESIGN AND METHODS-Two European population samples were studied: 1) one case-control cohort of 514 type I diabetic subjects and 2,027 control subjects and 2) one family cohort of 483 complete type I diabetic case-parent trios (total 997 affected). A total of 13 tag single nucleotide polymorphisms (SNPs) from the 10 type 2 diabetes loci were analyzed for type I diabetes association. RESULTS-No association of type 1 diabetes was found with any of the 10 type 2 diabetes loci, and no age-at-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 bordered on significance (P = 0.039) (odds ratio 0.929 [95% CI 0.867-0.995]), which did not reach the statistical significance threshold adjusted for 13 tests (a, 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.