TY - JOUR
T1 - A linkage study of 12 IDDM susceptibility loci in the Finnish population
AU - Laine, Antti-Pekka
AU - Nejentsev, Sergei
AU - Veijola, Riitta
AU - Korpinen, Eija
AU - Sjöroos, Minna
AU - Simell, Olli
AU - Knip, Mikael
AU - Åkerblom, Hans
AU - Ilonen, Jorma
PY - 2004
Y1 - 2004
N2 - 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 ≠ 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. Copyright © 2004 John Wiley and Sons, Ltd.
AB - 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 ≠ 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. Copyright © 2004 John Wiley and Sons, Ltd.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=1842843084&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/15037990
U2 - https://doi.org/10.1002/dmrr.424
DO - https://doi.org/10.1002/dmrr.424
M3 - Article
C2 - 15037990
SN - 1520-7552
VL - 20
SP - 144
EP - 149
JO - Diabetes/metabolism research and reviews
JF - Diabetes/metabolism research and reviews
IS - 2
ER -