Linkage of rheumatoid arthritis to insulin-dependent diabetes mellitus loci: Evidence supporting a hypothesis for the existence of common autoimmune susceptibility loci

Objective. To seek potential autoimmune disease susceptibility loci by testing for linkage and linkage disequilibrium between insulin-dependent diabetes mellitus (IDDM) susceptibility loci and rheumatoid arthritis (RA). Methods. Five IDDM susceptibility loci map to 2 chromosomal regions, chromosome 2q31-34 (IDDM7, 12, and 13) and chromosome 6q25-27 (IDDM5 and 8). Microsatellite markers within these regions were genotyped in 255 RA families, by fluorescence-based genotyping technology. Evidence for linkage disequilibrium was assessed using the extended transmission disequilibrium test (ETDT) program. Results. With the ETDT, we found evidence for linkage disequilibrium of the marker D6S446, at IDDM8, with RA (P <0.0001). There was additional evidence for linkage disequilibrium with 2 markers at IDDM5 (D6S311 and D6S440) (P = 0.016 and P = 0.017, respectively). There was no evidence for significant linkage disequilibrium of RA with any markers at IDDM7, 12, or 13. Conclusion. These results support the hypothesis that there are autoimmune disease genes at IDDM5 and IDDM8.