Autoimmune diseases in a Danish cohort of 4,866 carriers of constitutional structural chromosomal rearrangements

• Published in: Arthritis and rheumatism Vol. 56; no. 7; pp. 2402 - 2409
• Main Authors: Bache, Iben, Nielsen, Nete M., Rostgaard, Klaus, Tommerup, Niels, Frisch, Morten
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2007; Wiley
• Subjects: Anemias. Hemoglobinopathies; Autoimmune Diseases - epidemiology; Autoimmune Diseases - genetics; Biological and medical sciences; Chromosome Aberrations; Chromosomes, Human - genetics; Cohort Studies; Denmark; Diseases of red blood cells; Diseases of the osteoarticular system; Female; Follow-Up Studies; Gene Rearrangement; Hematologic and hematopoietic diseases; Humans; Inflammatory joint diseases; Juxtaarticular diseases. Extraarticular rhumatism; Male; Medical sciences; Denmark; Juxtaarticular disease; Immunopathology; Diseases of the osteoarticular system; Nutrition disorder; Vitamin deficiency; Juvenile rheumatoid arthritis; Autoimmune disease; Hemopathy; Inflammatory joint disease; B-Vitamins; Biermer disease; Cyanocobalamin; Chronic; Disease of the hand; Deletion; Dupuytren contracture; Danish; Upper limb
• ISSN: 0004-3591; 1529-0131
• DOI: 10.1002/art.22652

Objective Constitutional structural chromosomal rearrangements (CSCRs) have facilitated the identification of genes associated with early‐onset monogenic disorders and, more recently, genes associated with common and late‐onset disorders. In an attempt to find genetic clues to their etiologies, we studied the risk of autoimmune diseases in a Danish cohort of CSCR carriers. Methods We followed up 4,866 CSCR carriers over 71,230 person‐years (1980 through 2004) for autoimmune diseases recorded in the Danish Hospital Discharge Register. Standardized incidence ratios (SIRs) and 95% confidence intervals (95% CIs) served as measures of the relative risk. To identify possible candidate loci for autoimmune diseases, the reported chromosomal breakpoints and deletions in CSCR carriers who developed autoimmune diseases were compared with previously suggested loci for these diseases. Results The overall risk of any autoimmune disease among CSCR carriers was inconspicuous (SIR 1.2 [95% CI 0.95–1.5]; n = 74 cases observed versus 61.3 expected), but carriers of rearrangements involving chromosomes 2, 19, and 21 were at significantly increased risk. For the specific autoimmune diseases studied, cohort members were at significantly increased risk of Dupuytren's contracture, pernicious anemia, and juvenile rheumatoid arthritis (JRA). Sixteen carriers who developed an autoimmune disease had a chromosomal breakpoint or deletion coinciding with a previously suggested locus, including deletions 18p11, 18q22, and 22q11 associated with JRA. Conclusion CSCR carriers do not have a generalized predisposition to autoimmune diseases. However, we confirmed a number of reported susceptibility loci for JRA, and we suggest new susceptibility loci on chromosomes 5 and 11 for Dupuytren's contracture, and 19p13 as a possible shared susceptibility locus for a range of autoimmune diseases.