HLA-B27 and ankylosing spondylitis geographic distribution as the result of a genetic selection induced by malaria endemic? A review supporting the hypothesis.

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.

• Authors: Alessandro Mathieu, Alberto Cauli, Maria Teresa Fiorillo, Rosa Sorrentino
• Journal: Autoimmunity reviews (Autoimmun Rev) Vol. 7 Issue 5 Pg. 398-403 (May 2008) ISSN: 1568-9972 [Print] Netherlands
• PMID: 18486928 (Publication Type: Journal Article, Review)

Chemical References

• HLA Antigens
• HLA-B27 Antigen

Topics

• Endemic Diseases
• Gene Frequency
• Genetic Predisposition to Disease
• Geography
• HLA Antigens (genetics)
• HLA-B27 Antigen (genetics)
• Haplotypes
• Humans
• Malaria, Falciparum (epidemiology, genetics)
• Selection, Genetic
• Spondylitis, Ankylosing (epidemiology, genetics)