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 with HLA-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 / Alessandro, Mathieu; Alberto, Cauli; Fiorillo, Maria Teresa; Sorrentino, Rosa. - In: AUTOIMMUNITY REVIEWS. - ISSN 1568-9972. - 7:5(2008), pp. 398-403. [10.1016/j.autrev.2008.03.013]
HLA-B27 and Ankylosing Spondylitis geographic distribution as the result of a genetic selection induced by malaria endemic? A review supporting the hypothesis
FIORILLO, Maria Teresa;SORRENTINO, Rosa
2008
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 with HLA-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.