HLA-B27 POLYMORPHISM AND WORLDWIDE SUSCEPTIBILITY TO ANKYLOSING-SPONDYLITIS

HLA-B27 is strongly associated to ankylosing spondylitis (AS) and repr esents a family of eleven B27 alleles (B2701-11). Our aim was to anal yze the distribution of B27 subtypes by PCR/SSOP and genomic sequencin g in a large group of populations (n = 17). 711 B27-positive samples f rom Caucasoid, Asian, African, Amerindian and Polynesian populations w ere selected to ascertain transracial gene mapping of the B27 subtypes . 476 of these were AS patients, chosen to investigate the contributio n of B27 alleles to AS susceptibility. Some significant new findings h ave arisen from this study: 1) B2705 was the predominant subtype in c ircumpolar and subarctic areas. B2702 was found to be practically res tricted to Caucasian populations, showing a higher frequency in Middle -East (Jews) and North Africa (Arabs/Berbers) groups. 2) B2703 appear s associated with AS in Western Africans. This is of remarkable intere st since it was suggested that B2703 would be negatively disease-asso ciated. 3) Although B2706 appears negatively associated with AS in Th ais, we identified two patients from northern China carrying it. This may be a reflection of a disease heterogeneity and could indicate that more than one pathogenic agent can be involved in AS. B2709 has been recently described as negatively associated with AS in Sardinians. Th e molecular changes His114Asp (B2706) and Asp116His (B*2709) could mo dify the genetic susceptibility to AS.