Journal Article

Regulatory polymorphisms in <i>EGR2</i> are associated with susceptibility to systemic lupus erythematosus

Keiko Myouzen, Yuta Kochi, Kenichi Shimane, Keishi Fujio, Tomohisa Okamura, Yukinori Okada, Akari Suzuki, Tatsuya Atsumi, Satoshi Ito, Kazuki Takada, Akio Mimori, Shiro Ikegawa, Ryo Yamada, Yusuke Nakamura and Kazuhiko Yamamoto

in Human Molecular Genetics

Volume 19, issue 11, pages 2313-2320
Published in print June 2010 | ISSN: 0964-6906
Published online March 2010 | e-ISSN: 1460-2083 | DOI:
Regulatory polymorphisms in EGR2 are associated with susceptibility to systemic lupus erythematosus

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Systemic lupus erythematosus (SLE) is an autoimmune disease induced by the combinations of environmental and genetic factors. Recently, mice in which the early growth response 2 (EGR2) gene, a zinc-finger transcription factor, is conditionally knocked out in CD2+ T cells have been shown to develop a lupus-like autoimmune disease. Here, we evaluated if polymorphisms in the EGR2 gene influence SLE susceptibility in humans. We first analyzed the effect of SNPs in the EGR2 region on EGR2 expression, and a significant positive correlation with expression was identified in an SNP located at the 5′ flanking region of EGR2 (rs10761670, R=0.23, P=0.00072). We then performed a case–control association study using three sets of SLE cohorts by genotyping 14 tag SNPs in the EGR2 gene region. A peak of association with SLE susceptibility was observed for rs10761670 [Pooled: OR = 1.23 (95% CI 1.10–1.37), P=0.00023). This SNP was also associated with susceptibility to rheumatoid arthritis (RA) [OR = 1.15 (95% CI 1.05–1.26), P = 0.0019), suggesting that EGR2 is a common risk factor for SLE and RA. Among the SNPs in complete linkage disequilibrium with rs10761670 (r2 = 1.0), two SNPs (rs1412554 and rs1509957) affected the binding of transcription factors and transcriptional activity in vitro, suggesting that they may be candidates of causal regulatory variants in this region. Therefore, EGR2 is a genetic risk factor for SLE, in which increased gene expression may contribute to SLE pathogenesis.

Journal Article.  5155 words.  Illustrated.

Subjects: Genetics and Genomics

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