The geographic distribution of HLA-B27 shows a latitude-related gradient inverse to that of malaria endemic. An apparent exception occurs in New Guinea, a region where malaria is present, but where HLA-B27 frequency shows, however, an orographic gradient antithetic to that of malaria incidence. We therefore suggest that Plasmodium falciparum may have exerted a negative selection on this gene. This might be due to a higher susceptibility to severe forms of malaria, associated withHLA-B27 or other close gene(s). In addition, we suggest here that the same selective pressure that has contributed to reduce the HLA-B27 frequency in some regions has favoured the fixing of newly generated B27 subtypes included in more advantageous HLA haplotypes. In some cases, as for B⁎2709 in Sardinia and B⁎2706 in Southeast Asia, these haplotypes may harbour factors that protect from Ankylosing Spondylitis, an autoimmune disease strongly associated with HLA-B27, thus offering a novel, powerful tool to dissect disease pathogenesis, and to identify additional genetic factors of susceptibility. © 2008 Elsevier B.V. All rights reserved.
HLA-B27 and ankylosing spondylitis geographic distribution as the result of a genetic selection induced by malaria endemic? A review supporting the hypothesis
MATHIEU, ALESSANDRO;CAULI, ALBERTO;
2008-01-01
Abstract
The geographic distribution of HLA-B27 shows a latitude-related gradient inverse to that of malaria endemic. An apparent exception occurs in New Guinea, a region where malaria is present, but where HLA-B27 frequency shows, however, an orographic gradient antithetic to that of malaria incidence. We therefore suggest that Plasmodium falciparum may have exerted a negative selection on this gene. This might be due to a higher susceptibility to severe forms of malaria, associated withHLA-B27 or other close gene(s). In addition, we suggest here that the same selective pressure that has contributed to reduce the HLA-B27 frequency in some regions has favoured the fixing of newly generated B27 subtypes included in more advantageous HLA haplotypes. In some cases, as for B⁎2709 in Sardinia and B⁎2706 in Southeast Asia, these haplotypes may harbour factors that protect from Ankylosing Spondylitis, an autoimmune disease strongly associated with HLA-B27, thus offering a novel, powerful tool to dissect disease pathogenesis, and to identify additional genetic factors of susceptibility. © 2008 Elsevier B.V. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.