IDDM12 (CTLA4) on 2q33 and IDDM13 on 2q34 in genetic susceptibility to type 1 diabetes (insulin-dependent)

Type 1 diabetes (insulin-dependent) is a multifactorial disease with polyge nic susceptibility;, The major genetic component (IDDM1) resides within the HLA region, but several non-HLA loci have been implicated in the genetic s usceptibility, In the present study, we have analysed two such loci, IDDM12 (CTLA4) on 2q33 and IDDM13 on 2q34, in Danish (n = 254) and Spanish (n = 3 9) type 1 diabetic multiplex families. No significant evidence of Linkage o f IDDM12 was observed in any of the two studied data sets, However, when th e present data were combined with previously published data, they strengthe ned the evidence of linkage at this locus, p = 0.00002. For the IDDM13 regi on, we found some positive evidence of linkage of the D2S137-D2S164-D2S1471 markers (p-values 0.007, 0.02, and 0.007, respectively) using transmission disequilibrium testing (TDT) and the T-sp version of the TDT, Importantly, random transmission of all tested alleles was observed in unaffected offsp ring (p > 0.3), Stratification for HLA thigh risk and non-high risk genotyp es) in the Danish families did not reveal heterogeneity at IDDM12 or IDDIM1 3, In conclusion, our data on an entirely new family data set did not suppo rt the existence of IDDM12 as a type 1 diabetes susceptibility locus in the Danish population, In addition, we found support for evidence of linkage a nd association of the IDDM13/D2S137-D2S1471 region (approximately 3.5 cM) t o type 1 diabetes, however, further studies are needed to substantiate this observation.