The IDDM13 region containing the insulin-like growth factor binding protein-5 (IGFBP5) gene on chromosome 2q33-q36 and the genetic susceptibility to rheumatoid arthritis.
We considered that the constitutive over-expression by cultured rheumatoid arthritis (RA) fibroblast-lineage synoviocytes of genes like IGFBP5 could indicate new candidate susceptibility genes. IGFBP5 is located in a region where an insulin-dependent diabetes mellitus (IDDM) susceptibility locus, IDDM13 (2q33-q36), has been mapped. Previous evidence that non-MHC IDDM loci overlap RA susceptibility loci made IGFBP5 and its region an interesting candidate locus which was tested for linkage. Forty-nine sibships (2-4 affected siblings per sibship) with RA were genotyped with microsatellite markers covering an 11.2 cM interval in the IGFBP5/IDDM13 region. Both the two-point LOD scores and a 'nonparametric' allele-sharing analysis revealed no evidence for linkage (max LOD = 0.54, P = 0.5, respectively). Adjustments for the presence of 'shared-epitope' alleles did not significantly change the LOD scores. These results suggest that, despite the involvement of the 2q33-q36 chromosomal region in another organ-specific autoimmune disease, it is unlikely that this region harbors a RA susceptibility locus.
Slager
S L
SL
New York Psychiatric Institute, Department of Psychiatry adn Department of Biostatistics, Columbia University College of Physicians and Surgeons, New York, NY, USA.
Carleu
L
L
Chung
W K
WK
Jackson
T
T
Winchester
R J
RJ
Hodge
S E
SE
Gulko
P S
PS
D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics*; D008297:Male; D008875:Middle Aged
D018975:Insulin-Like Growth Factor Binding Protein 5