Volume 12 Supplement 1
Prevalence of polymorphisms of the genes responsible for auto-inflammatory diseases among 202 patients with recurrent fever in a rheumatology institute in Japan
© Miyamae et al; licensee BioMed Central Ltd. 2014
Published: 17 September 2014
Auto-inflammatory syndromes are defined as conditions caused by an exaggerated innate immune system response, resulting in episodes of spontaneous inflammation affecting multiple organs. The prototypical auto-inflammatory disorders are associated with periodic febrile episodes. Auto-inflammatory syndromes now include polygenic diseases, such as Behcet's syndrome and Still's disease; however, the best characterized auto-inflammatory diseases are relatively rare, but florid conditions arising from mutations in single genes. The prevalence of each auto-inflammatory disease varies depending on ethnic background.
To analyze the prevalence of polymorphisms of the genes responsible for auto-inflammatory diseases managed in a single rheumatology institute in Japan.
A total of 202 individuals < 40 years of age with recurrent febrile episodes were enrolled in this study. Recurrent fever was defined as > 2 episodes of fever > 38.5 degrees Celsius lasting > 3 days in a year. Infections, autoimmune disorders, and malignancies were excluded as causes of fever prior to enrollment. Genomic DNA was isolated from the patients’ peripheral blood and a polymerase chain reaction (PCR) was used to amplify the indicated exons of 10 genes [MEFV (exons 1-10), TNFRSF1A (exons 2-4), MVK (exons 9-11), NLRP3 (exon 3), NOD2 (exon 4), LI1RN (exons 2-4), IL36RN (exons 2-5), PSMB8 (exons 2, 3, and 5), NALP12 (exons 3 and 9), and PSTPIP1 (exons 10 and 11)], which have been reported as the genes responsible for auto-inflammatory diseases. After cleaning the PCR products, cycle sequencing was carried out using the Big Dye® Terminator v3.1 kit and analyzed with an ABI 3130xl Prism Genetic Analyzer. For the most frequently reported 4 genes, genetic polymorphisms within MEFV (exons 1-10), TNFRSF1A (exons 2-4), MVK (exons 9-11), and NLRP3 (exon 3) were examined. With respect to the other 6 genes, the existence of polymorphisms was also determined within NOD2 (from L248R to P727L), LI1RN (from N52KfsX25 to C91F), IL36RN (from R10X to G141Mfs*29), PSMB8 (from T75M to G201V), NALP12 (from T260M to F402L and R1016X), and PSTPIP1 (from A230T to E277D), with reference to the INFEVERS database, an evolving mutation database for auto-inflammatory syndromes (http://fmf.igh.cnrs.fr/ISSAID/infevers/index.php).
Gene polymorphisms in the targeted genes were identified in 116 of the 202 patients (57%) based on INFEVERS. One hundred four of the 116 polymorphisms (90.0%) were associated with MEFV genes. Other polymorphisms were identified in TNFRSF1A (n=7), NLRP3 (n=5), NOD2 (n=4), MVK (n=2), and PSTPIP1 (n=1).
Polymorphisms in MEFV were most frequently identified among Japanese patients with recurrent fevers.
Disclosure of interest
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.