TY - JOUR
T1 - Regulatory polymorphisms in EGR2 are associated with susceptibility to systemic lupus erythematosus
AU - Myouzen, Keiko
AU - Kochi, Yuta
AU - Shimane, Kenichi
AU - Fujio, Keishi
AU - Okamura, Tomohisa
AU - Okada, Yukinori
AU - Suzuki, Akari
AU - Atsumi, Tatsuya
AU - Ito, Satoshi
AU - Takada, Kazuki
AU - Mimori, Akio
AU - Ikegawa, Shiro
AU - Yamada, Ryo
AU - Nakamura, Yusuke
AU - Yamamoto, Kazuhiko
N1 - Funding Information:
This work was supported by grants from the CGM, RIKEN; the Ministry of Education, Culture, Sports, Science and Technology of Japan (Leading Project); and the Ministry of Health, Labor and Welfare of Japan (Research on Intractable Diseases).
PY - 2010/3/1
Y1 - 2010/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77953514276&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddq092
DO - 10.1093/hmg/ddq092
M3 - Article
C2 - 20194224
AN - SCOPUS:77953514276
SN - 0964-6906
VL - 19
SP - 2313
EP - 2320
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 11
M1 - ddq092
ER -