A linkage study of 12 IDDM susceptibility loci in the Finnish population.
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.
Laine
Antti-Pekka
AP
JDRF Centre for Prevention of Type 1 Diabetes in Finland, Department of Virology, University of Turku, Turku, Finland. aplaine@utu.fi
Nejentsev
Sergei
S
Veijola
Riitta
R
Korpinen
Eija
E
Sjöroos
Minna
M
Simell
Olli
O
Knip
Mikael
M
Akerblom
Hans K
HK
Ilonen
Jorma
J
D002877:Chromosomes, Human / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D005260:Female; D005387:Finland; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006680:HLA Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006650:Histocompatibility Testing; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics*
D005819:Genetic Markers; D006680:HLA Antigens; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen