NDLI: Association of Functional Polymorphisms in Interferon Regulatory Factor 2 (IRF2) with Susceptibility to Systemic Lupus Erythematosus: A Case-Control Association Study

Content Provider	PubMed Central
Author	Kawasaki, Aya Furukawa, Hiroshi Nishida, Nao Warabi, Eiji Kondo, Yuya Ito, Satoshi Matsumoto, Isao Makio, Kusaoi Amano, Hirofumi Suda, Akiko Nagaoka, Shouhei Setoguchi, Keigo Nagai, Tatsuo Hirohata, Shunsei Shimada, Kota Sugii, Shoji Okamoto, Akira Chiba, Noriyuki Suematsu, Eiichi Ohno, Shigeru Katayama, Masao Okamoto, Akiko Kono, Hajime Tokunaga, Katsushi Takasaki, Yoshinari Hashimoto, Hiroshi Sumida, Takayuki Tohma, Shigeto Tsuchiya, Naoyuki
Editor	Montgomery, Courtney G.
Copyright Year	2014
Abstract	Interferon regulatory factor 2 (IRF2) negatively regulates type I interferon (IFN) responses, while it plays a role in induction of Th1 differentiation. Previous linkage and association studies in European-American populations suggested genetic role of IRF2 in systemic lupus erythematosus (SLE); however, this observation has not yet been confirmed. No studies have been reported in the Asian populations. Here we investigated whether IRF2 polymorphisms contribute to susceptibility to SLE in a Japanese population. Association study of 46 IRF2 tag single nucleotide polymorphisms (SNPs) detected association of an intronic SNP, rs13146124, with SLE. When the association was analyzed in 834 Japanese patients with SLE and 817 healthy controls, rs13146124 T was significantly increased in SLE compared with healthy controls (dominant model, P = 5.4×10−4, Bonferroni-corrected P [Pc] = 0.026, odds ratio [OR] 1.48, 95% confidence interval [CI] 1.18–1.85). To find causal SNPs, resequencing was performed by next-generation sequencing. Twelve polymorphisms in linkage disequilibrium with rs13146124 (r2: 0.30–1.00) were identified, among which significant association was observed for rs66801661 (allele model, P = 7.7×10−4, Pc = 0.037, OR 1.53, 95%CI 1.19–1.96) and rs62339994 (dominant model, P = 9.0×10−4, Pc = 0.043, OR 1.46, 95%CI 1.17–1.82). The haplotype carrying both of the risk alleles (rs66801661A–rs62339994A) was significantly increased in SLE (P = 9.9×10−4), while the haplotype constituted by both of the non-risk alleles (rs66801661G–rs62339994G) was decreased (P = 0.0020). A reporter assay was carried out to examine the effect of the IRF2 haplotypes on the transcriptional activity, and association of the IRF2 risk haplotype with higher transcriptional activity was detected in Jurkat T cells under IFNγ stimulation (Tukey's test, P = 1.2×10−4). In conclusion, our observations supported the association of IRF2 with susceptibility to SLE, and the risk haplotype was suggested to be associated with transcriptional activation of IRF2.
Related Links	http://dx.doi.org/10.1371/journal.pone.0109764
Starting Page	109764
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	10
Volume Number	9
Language	English
Publisher	Public Library of Science
Publisher Date	2014-10-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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