Abstract
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 (∼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 (∼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.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
McDermott MF, Aksentijevich I, Galon J et al: Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell 1999; 97: 133–144.
Aksentijevich I, Galon J, Soares M et al: The tumor-necrosis-factor receptor-associated periodic syndrome: new mutations in TNFRSF1A, ancestral origins, genotype–phenotype studies, and evidence for further genetic heterogeneity of periodic fevers. Am J Hum Genet 200; 69: 301–314.
Dode C, Andre M, Bienvenu T et al: The enlarging clinical, genetic, and population spectrum of tumor necrosis factor receptor-associated periodic syndrome. Arthritis Rheum 2002; 46: 2181–2188.
Arkwright PD, McDermott MF, Houten SM et al: Hyper IgD syndrome (HIDS) associated with in vitro evidence of defective monocyte TNFRSF1A shedding and partial response to TNF receptor blockade with etanercept. Clin Exp Immunol 2002; 130: 484–488.
Dode C, Papo T, Fieschi C et al: A novel missense mutation (C30S) in the gene encoding tumor necrosis factor receptor 1 linked to autosomal-dominant recurrent fever with localized myositis in a French family. Arthritis Rheum 2000; 43: 1535–1542.
Aganna E, Hammond L, Hawkins PN et al: Heterogeneity among patients with tumor necrosis factor receptor-associated periodic syndrome phenotypes. Arthritis Rheum 2003; 48: 2632–2644.
Segal S, Hill AV : Genetic susceptibility to infectious disease. Trends Microbiol 2003; 11: 445–448.
Rothe J, Lesslauer W, Lotscher H et al: Mice lacking the tumour necrosis factor receptor 1 are resistant to TNF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes. Nature 1999; 364: 798–802.
Keane J, Gershon S, Wise RP et al: Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 2001; 345: 1098–1104.
Mombo LE, Ntoumi F, Bisseye C et al: Human genetic polymorphisms and asymptomatic Plasmodium falciparum malaria in Gabonese schoolchildren. Am J Trop Med Hyg 2003; 68: 186–190.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tchernitchko, D., Chiminqgi, M., Galactéros, F. et al. Unexpected high frequency of P46L TNFRSF1A allele in sub-Saharan West African populations. Eur J Hum Genet 13, 513–515 (2005). https://doi.org/10.1038/sj.ejhg.5201344
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/sj.ejhg.5201344
Keywords
This article is cited by
-
Canakinumab efficacy and long-term tocilizumab administration in tumor necrosis factor receptor-associated periodic syndrome (TRAPS)
Rheumatology International (2015)
-
The labyrinth of autoinflammatory disorders: a snapshot on the activity of a third-level center in Italy
Clinical Rheumatology (2015)
-
Trauma Induced Inflammation, Sepsis and Ageing
Ageing International (2014)
-
Dramatic etanercept-induced remission of relapsing febrile sciatic neuralgia related to p46l mutation of the tnfrsf1a gene
Clinical Rheumatology (2007)
