HLA-B27 alone rather than B27-related class I haplotypes contributes to ankylosing spondylitis susceptibility

Characterization of non-B27 susceptibility genes will be required to know t he pathogenesis of AS. The aim of this study was to examine whether ankylos ing spondylitis (AS) susceptibility is controlled by B27 alone rather than B27 haplotypes and, whether ocher closely related class I loci, such as MIC A and TNFA genes might play a role in AS, Three hundred eleven B27-positive samples from Caucasoid, Asian, and African populations were selected and g enotypes were carried out by PCR/ SSOP (HLA-B27 and HLA-C), PCR/SSP (MICA-T M polymorphism in the transmembrane region), PCR/SSCP (MICA alleles), and P CR-RFLP (TNF-alpha). Of these, 161 were AS patients, chosen in order to inv estigate the contribution of TNFA and MICA loci to AS in HLA-B27 positive i ndividuals. Some findings can be concluded from the study: (a) No significa nt differences of TNF-alpha promoter alleles at position -308 and -238 (A/G ) were found between AS patients and B27 matched alleles from healthy contr ols; (b) strong linkage disequilibrium was found between the B27 and the MI CA alleles. The MICA-A4 was found co be in association with B*2705,02,03 an d 08; MICA-A5 with B*2704 and B*2707 and MICA-A.5.1 with B*2706; (c) no sig nificant differences of MICA alleles were found between AS and controls car rying the B27-associated alleles, and therefore no evidence is provided for an additional role of MICA gene in AS susceptibility; (d) there are a stri king correlations between the structure of B27 extended haplotypes (from MI CA region to HLA-C) and the ethnic distribution of these subtypes. The resu lts of differential linkage disequilibrium with HLA-B27 subtypes suggest th at B27 itself remains the primary gene for AS susceptibility, and TNFA and MICA are nor involved in the pathogenesis of the disease, Human Immunology 61, 131-139 (2000). (C) American Society for Histocompatibility and Immunog enetics, 2000. Published by Elsevier Science Inc.