PMID- 20194224
OWN - NLM
STAT- MEDLINE
DCOM- 20100922
LR  - 20100507
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Linking)
VI  - 19
IP  - 11
DP  - 2010 Jun 1
TI  - Regulatory polymorphisms in EGR2 are associated with susceptibility to systemic 
      lupus erythematosus.
PG  - 2313-20
LID - 10.1093/hmg/ddq092 [doi]
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 (r(2) = 
      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.
FAU - Myouzen, Keiko
AU  - Myouzen K
AD  - Laboratory for Autoimmune Diseases, Center for Genomic Medicine, RIKEN, Tokyo 
      113-0033, Japan.
FAU - Kochi, Yuta
AU  - Kochi Y
FAU - Shimane, Kenichi
AU  - Shimane K
FAU - Fujio, Keishi
AU  - Fujio K
FAU - Okamura, Tomohisa
AU  - Okamura T
FAU - Okada, Yukinori
AU  - Okada Y
FAU - Suzuki, Akari
AU  - Suzuki A
FAU - Atsumi, Tatsuya
AU  - Atsumi T
FAU - Ito, Satoshi
AU  - Ito S
FAU - Takada, Kazuki
AU  - Takada K
FAU - Mimori, Akio
AU  - Mimori A
FAU - Ikegawa, Shiro
AU  - Ikegawa S
FAU - Yamada, Ryo
AU  - Yamada R
FAU - Nakamura, Yusuke
AU  - Nakamura Y
FAU - Yamamoto, Kazuhiko
AU  - Yamamoto K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100301
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (EGR2 protein, human)
RN  - 0 (Early Growth Response Protein 2)
SB  - IM
MH  - Case-Control Studies
MH  - Early Growth Response Protein 2/*genetics/metabolism
MH  - Electrophoretic Mobility Shift Assay
MH  - Gene Expression Regulation/*genetics
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genome-Wide Association Study
MH  - Genotype
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Lupus Erythematosus, Systemic/*genetics
MH  - Polymorphism, Single Nucleotide/*genetics
EDAT- 2010/03/03 06:00
MHDA- 2010/09/24 06:00
CRDT- 2010/03/03 06:00
PHST- 2010/03/03 06:00 [entrez]
PHST- 2010/03/03 06:00 [pubmed]
PHST- 2010/09/24 06:00 [medline]
AID - ddq092 [pii]
AID - 10.1093/hmg/ddq092 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2010 Jun 1;19(11):2313-20. doi: 10.1093/hmg/ddq092. Epub 2010 Mar 
      1.