ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 87

Association of TRIM21 (RO52) Polymorphisms with Systemic Lupus Erythematosus in a Japanese Population

Misaki Hidaka1, Aya Kawasaki1, Hiroshi Furukawa2, Yuya Kondo3, Satoshi Ito4, Isao Matsumoto5, Makio Kusaoi6, Hirofumi Amano6, Akiko Suda7, Keigo Setoguchi8, Tatsuo Nagai9, Kota Shimada10, Shoji Sugii10, Akira Okamoto11, Noriyuki Chiba12, Eiichi Suematsu13, Masao Katayama14, Akiko Okamoto15, Hajime Kono15, Shigeru Ohno7, Shunsei Hirohata16, Shouhei Nagaoka17, Yoshinari Takasaki18, Hiroshi Hashimoto19, Shigeto Tohma2, Takayuki Sumida3 and Naoyuki Tsuchiya1, 1Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan, 2Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara, Japan, 3Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan, 4Department of Rheumatology, Niigata Rheumatic Center, Shibata, Japan, 5Department of Interenal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan, 6Department of Rheumatology and Internal Medicine, Juntendo University, Tokyo, Japan, 7Center for Rheumatic Diseases, Yokohama City University Medical Center, Yokohama, Japan, 8Allergy and Immunological Diseases, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan, 9Department of Rheumatology and Infectious Diseases, Kitasato University School of Medicine, Sagamihara, Japan, 10Department of Rheumatic Diseases, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan, 11Department of Rheumatology,, Himeji Medical Center, National Hospital Organization, Himeji, Japan, 12Department of Rheumatology, Morioka Hospital, National Hospital Organization, Morioka, Japan, 13Department of Internal Medicine and Rheumatology, Clinical Research Institute, Kyushu Medical Center, National Hospital Organization, Fukuoka, Japan, 14Division of Rheumatology, Department of Internal Medicine, Nagoya Medical Center, National Hospital Organization, Nagoya City, Aichi, Japan, 15Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan, 16Int Med/Rheumatol & Infec Dis, Kitasato University School of Medicine, Sagamihara, Japan, 17Department of Rheumatology, Yokohama Minami Kyousai Hospital, Yokohama, Japan, 18Department of Rheumatology, Juntendo University School of Medicine, Tokyo, Japan, 19Juntendo University School of Medicine, Tokyo, Japan

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: , ,

Session Information

Title: Genetics, Genomics and Proteomics I

Session Type: Abstract Submissions (ACR)

Background/Purpose

TRIM21, also referred to as Ro52 or SS-A1, belongs to the tripartite motif-containing (TRIM) family. TRIM21 is not only important as an autoantigen, but also as a component of the signaling pathway relevant to the disease processes of autoimmune rheumatic diseases. TRIM21 is induced by type I interferon, ubiquitylates proteins of the interferon-regulatory factor (IRF) family, and regulates type I interferon and proinflammatory cytokines. Furthermore, TRIM21 has also been reported to function as an intracellular Fc receptor. To date, it is not clear how these different aspects of TRIM21 are functionally related. Until now, several very small scale studies suggested the association of some SNPs in TRIM21 with susceptibility to systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SS). However, to our knowledge, systematic association study covering all the tagSNPs has not been reported. In this study, we conducted a systematic association study between SLE andTRIM21in a Japanese case-control set with more than 1,000 individuals.

Methods

Nine tagSNPs in TRIM21 region were selected based on JPT HapMap data with the criteria of minor allele frequency > 0.05 and r2 threshold of 0.80. 530 Japanese SLE and 518 healthy Japanese controls were genotyped for the tagSNPs using TaqMan allele discrimination assay, and case-control association study was performed. Prediction of functional relevance of the SNPs was done by using SNP Function Prediction (FuncPred) website (http://snpinfo.niehs.nih.gov/snpinfo/snpfunc.htm). This study was reviewed and approved by the ethics committees of each participating institute. Informed consent was provided by all subjects.

Results

Among the 9 tagSNPs,  association was detected in 3 SNPs. At rs7947461 in intron 1, the frequency of T allele (P=0.04, odds ratio [OR] 0.76, 95% confidence interval [CI] 0.58-0.98) and that of the T/T genotype (P=0.04, OR 0.72, 95% CI 0.53-0.99) were decreased. At rs9261010 in exon 2 coding for a synonymous substitution, T allele frequency (P=0.04, OR 0.81, 95%CI 0.67-0.99) and T/T genotype frequency (P=0.05, OR 0.62, 95% CI 0.39-1.00) were decreased. Furthermore, at rs4144331 in the 3’ untranslated region (UTR), decrease in T allele frequency (P=0.04, OR 0.76, 95%CI 0.58-0.98) and in T/T genotype frequency (P=0.04, OR 0.75, 95% CI 0.56-0.99) were observed. A bioinformatic analysis predicted that rs4144331 may affect binding of miRNA hsa-miR-1300.

Conclusion

These results suggested that of TRIM21 polymorphisms may be associated with susceptibility to SLE. Further replication studies as well as functional studies are required.

Disclosure:

M. Hidaka,
None;

A. Kawasaki,
None;

H. Furukawa,
None;

Y. Kondo,
None;

S. Ito,
None;

I. Matsumoto,
None;

M. Kusaoi,
None;

H. Amano,
None;

A. Suda,
None;

K. Setoguchi,
None;

T. Nagai,
None;

K. Shimada,
None;

S. Sugii,
None;

A. Okamoto,
None;

N. Chiba,
None;

E. Suematsu,
None;

M. Katayama,
None;

A. Okamoto,
None;

H. Kono,
None;

S. Ohno,
None;

S. Hirohata,
None;

S. Nagaoka,
None;

Y. Takasaki,
None;

H. Hashimoto,
None;

S. Tohma,
None;

T. Sumida,
None;

N. Tsuchiya,
None.

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