A linkage study of 12 IDDM susceptibility loci in the Finnish population

Abstract

Background: HLA region is the major locus (IDDM1) of type 1 diabetes (T1D) susceptibility. It explains approximately 50% of the genetic background of T1D, indicating additional genetic determinants. Genome scans and candidate gene studies have generated several chromosomal candidate regions that may have a role in T1D development.

Methods: We tested 12 of these loci for linkage in 107 Finnish T1D multiplex families using 23 microsatellite markers and 2 SNPs. Families were stratified according to the HLA status and sharing at the DQB1 gene.

Results: We found no significant or suggestive MLS in our unstratified families outside the IDDM1 locus. The highest MLS was seen close to the IDDM9 region marker D3S3576 at 3q21-q25 (MLS=1.05). This marker also had a global p-value of 0.0032 (ETDT) in maternal transmissions. IDDM6 and 12q12-q15 region showed MLS=1.1 and MLS=1.3 respectively in HLA-DQB1*0302/x (x is not equal to HLA-DQB1*02) stratified families. IDDM12 showed MLS=2.0 in HLA-DQB1 identical sib pairs. Linkage at IDDM12 was supported by a global p-value of 0.0006 (uncorrected) in ETDT. For IDDM2, p-values of 0.028 and 0.009 were observed in ETDT with MspI-2221 SNP in unstratified and HLA-DQB1*0302/x-stratified families respectively.

Conclusions: Our results are consistent with previous findings of linkage or association to T1D at IDDM2, IDDM6, IDDM9, IDDM12 and 12q12-q15 regions but do not unambiguously confirm them. A larger sample set is required to gain statistical power needed to confirm our findings in the Finnish population.