Suggestive evidence for association of human chromosome 18q12-q21 and its orthologue on rat and mouse chromosome 18 with several autoimmune diseases.
2001
Some immune system disorders, such as type 1 diabetes, multiple sclerosis
(MS), and rheumatoid arthritis (RA), share common features: the presence of
autoantibodies and self-reactive T-cells, and a genetic association with the
major histocompatibility complex. We have previously published evidence, from
1,708 families, for linkage and association of a haplotype of three markers in
the D18S487 region of chromosome 18q21 with type 1 diabetes. Here,
the three markers were typed in an independent set of 627 families and,
although there was evidence for linkage (maximum logarithm of odds score [MLS]
= 1.2; P = 0.02), no association was detected. Further linkage
analysis revealed suggestive evidence for linkage of chromosome 18q21 to type
1 diabetes in 882 multiplex families (MLS = 2.2; λs = 1.2; P =
0.001), and by meta-analysis the orthologous region (also on chromosome 18) is
linked to diabetes in rodents ( P = 9 × 10 -4 ). By
meta-analysis, both human chromosome 18q12-q21 and the rodent orthologous
region show positive evidence for linkage to an autoimmune phenotype
( P = 0.004 and 2 × 10 -8 , respectively, empirical P = 0.01 and 2 × 10 -4 , respectively). In the
diabetes-linked region of chromosome 18q12-q21, a candidate gene, deleted in
colorectal carcinoma (DCC), was tested for association with human autoimmunity
in 3,380 families with type 1 diabetes, MS, and RA. A haplotype
(“2-10”) of two newly characterized microsatellite markers within DCC showed evidence for association with autoimmunity ( P = 5
× 10 -6 ). Collectively, these data suggest that a locus (or
loci) exists on human chromosome 18q12-q21 that influences multiple autoimmune
diseases and that this association might be conserved between species.
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