Unexpected high frequency of P46L TNFRSF1A allele in sub-Saharan West African populations

Eur J Hum Genet. 2005 Apr;13(4):513-5. doi: 10.1038/sj.ejhg.5201344.


TNF receptor-associated periodic syndrome (TRAPS) is an autosomal dominant disorder characterized by recurrent attacks of fever and serositis. To date, more than 30 mutations have been reported in TNFRSF1A, the responsible gene. In Caucasian populations, the P46L (c.224C>T) TNFRSF1A sequence variation is considered as a low-penetrance mutation because its allele frequency is similar in patients and controls ( approximately 1%). Whereas the spectrum of TNFRSF1A gene mutations has been well established in Caucasian and several Mediterranean populations, it remains unknown in sub-Saharan African populations. In this study, we found an unexpected high P46L allele frequency ( approximately 10%) in two groups from West Africa - a group of 145 patients with sickle cell anaemia and a group of 349 healthy controls. These data suggest that the P46L variant is rather a polymorphism than a TRAPS causative mutation. We propose that the P46L high frequency in West African populations could be explained by some biological advantage conferred to carriers.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Anemia, Sickle Cell / genetics*
  • Black People
  • Case-Control Studies
  • DNA Mutational Analysis
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Mutation / genetics*
  • Penetrance
  • Receptors, Tumor Necrosis Factor, Type I / genetics*


  • Receptors, Tumor Necrosis Factor, Type I