Lie_2007_Hum.Immunol_68_592

We have previously mapped a separate type 1 diabetes (T1D) association in the extended MHC class I region, marked by D6S2223, on the DRB1*03-DQA1*0501-DQB1*0201 haplotype. The associated region encompasses a gene encoding a thymus-specific serine protease (PRSS16), presumably involved in positive selection of T cells or in T-cell regulation. Fourteen PRSS16 polymorphisms were genotyped in two steps using a total of six T1D family data sets, as well as case-control materials for both T1D and celiac disease (CD). An association with a 15 base-pair deletion in exon 12 of PRSS16 was found on the DRB1*03-DQA1*0501-DQB1*0201 haplotype for both T1D and CD, but it could not explain the more pronounced disease associations observed at marker D6S2223. We compared the performance of the 14 tested PRSS16 polymorphisms, selected after our previous comprehensive screen, against HapMap selected tag SNPs. Use of a HapMap based SNP selection strategy would result in loss of a large proportion of the genetic variation in PRSS16. Our data suggest that it is unlikely that polymorphisms within the PRSS16 gene are involved in the predisposition to T1D. However, we cannot rule out that regulatory polymorphisms located some distance away from the gene may be involved.