Which HLA shows a strong association with AS? Does this association vary among different racial groups?
HLA-B27 is present in 90% of white AS patients and in 50% to 80% of nonwhite AS patients. The prevalence of the HLA-B27 allele is 6% to 9% in healthy whites and 3% in healthy North American blacks. Consequently, an HLA-B27-positive individual has a 50 to 75 times increased relative risk of developing AS compared with HLA-B27-negative individuals. For white patients, this translates into a sensitivity of 90%, positive predictive value of only 5.6%, and a negative predictive value of 99.9%. This means that a positive test is of fairly modest benefit and a negative test is good for ruling out disease, though test characteristics are generally poorer for most nonwhite patients.
Twin studies show a 60% to 75% disease concordance for AS in monozygotic twins and a 12% to 27% disease concordance in HLA-B27 dizygotic twins. By this analysis, genetics contributes 90% to the total risk for developing AS. HLA-B27 contributes 25% to 40% to the heritability of the disease. Thus, other genetic factors must be contributing to the risk of developing AS in addition to environmental factors. Over 30 non-HLA-B genetic loci have been identified, including ERAP-1 and IL-23R. None of these are remotely as important as HLA-B27. Genetic associations with axSpA are considerably weaker than those for AS in particular. Genetic risk scores are in development.