HLA-B27 and ankylosing spondylitis geographic distribution as the result of a genetic selection induced by malaria endemic? A review supporting the hypothesis.
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.
Mathieu
Alessandro
A
Department of Medical Sciences, University of Cagliari, SS 554, 09042 Monserrato, Cagliari, Italy. mathieu@pacs.unica.it
Cauli
Alberto
A
Fiorillo
Maria Teresa
MT
Sorrentino
Rosa
R
D019353:Endemic Diseases; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005843:Geography; D006680:HLA Antigens / Q000235:genetics; D015796:HLA-B27 Antigen / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000235:genetics*; D012641:Selection, Genetic; D013167:Spondylitis, Ankylosing / Q000453:epidemiology* / Q000235:genetics*
D006680:HLA Antigens; D015796:HLA-B27 Antigen