SUSCEPTIBILITY TO ANKYLOSING-SPONDYLITIS IN TWINS - THE ROLE OF GENES, HLA, AND THE ENVIRONMENT

Objective. To determine the relative effects of genetic and environmen tal factors in susceptibility to ankylosing spondylitis (AS). Methods. Twins with AS were identified from the Royal National Hospital for Rh eumatic Diseases database, Clinical and radiographic examinations were performed to establish diagnoses, and disease severity was assessed u sing a combination of validated scoring systems, HLA typing for HLA-B2 7, HLA-B60, and HLA-DR1 was performed by polymerase chain reaction wit h sequence-specific primers, and zygosity was assessed using microsate llite markers, Genetic and environmental variance components were asse ssed with the program Mx, using data from this and previous studies of twins with AS. Results. Six of 8 monozygotic (MZ) twin pairs were dis ease concordant, compared with 4 of 15 B27-positive dizygotic (DZ) twi n pairs (27%) and 4 of 32 DZ twin pairs overall (12.5%). Nonsignifican t increases in similarity with regard to age at disease onset and all of the disease severity scores assessed were noted in disease-concorda nt MZ twins compared with concordant DZ twins, HLA-B27 and B60 were as sociated with the disease in probands, and the rate of disease concord ance was significantly increased among DZ twin pairs in which the co-t win was positive for both B27 and DR1. Additive genetic effects were e stimated to contribute 97% of the population variance, Conclusion. Sus ceptibility to AS is largely genetically determined, and the environme ntal trigger for the disease is probably ubiquitous. HLA-B27 accounts for a minority of the overall genetic susceptibility to AS.