Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Association Analysis of EGR2 Gene with SLE Susceptibility
Myouzen1, Keiko, Kochi1, Yuta, Shimane1, Kenichi, Suzuki1, Akari, Fujio2, Keishi, Okamura2, Tomohisa, Yamada3, Ryo
Laboratory for Autoimmune diseases, Center for Genomic Medicine, The Institute of Physical and Chemical Research (RIKEN). Tokyo, Japan
Department of Allergy and Rheumatology.Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Laboratory of Functional Genomics, Human Genome Center, The Institute of Medical science, The University of Tokyo, Toyko, Japan
Laboratory of Molecular Medicine, Human Genome Center, The Institute of Medical science, The University of Tokyo, Tokyo, Japan
Early growth response 2 (EGR2) gene is a zinc-finger transcription factor, whose knockout in mice has been shown to develop a lupus-like autoimmune disease. We performed case-control association study to analyze the association of EGR2 with SLE susceptibility in Japanese population.
We selected 20 tag SNPs from 80 kb region including EGR2 and genotyped them using TaqMan assays. We compared the allele frequency of SNPs between two sets of case-control subjects in Japanese population (1st set, 376 SLE patients and 940 controls; 2nd set, 243 SLE patients and 881 controls). We analyzed the correlation between EGR2 expression and SNP genotypes in EBV-transformed lymphoblastoid cell lines from HapMap individuals. We also performed luciferase assays to assess the transcriptional enhancer and repressor activity of DNA sequences surrounding the disease-associated SNPs.
We identified a significant association of rs10761670 (A/T; T allele was susceptible allele) in the 5' flank region of EGR2 with SLE susceptibility (1st set: p=0.049, OR=1.19 [95%CI 1.001.41]; 2nd set: p=0.029, OR=1.22 [95%CI 1.021.53] and pooled: p=0.0036, OR=1.22 [95%CI 1.071.39]). We also found a significant positive correlation between the number of susceptible alleles of rs10761670 and the transcriptional level of EGR2 (R=0.23, p=0.0007). Among the SNPs in complete disequilibrium with rs10761670 (r2=1.0), two SNPs (rs1412554 and rs1509957) affected transcriptional activity in luciferase assays, and thus they could be candidates for causal variants in this region.
EGR2 is a genetic risk factor for SLE, in which increased gene expression may contribute to SLE pathogenesis.
To cite this abstract, please use the following information:
Myouzen, Keiko, Kochi, Yuta, Shimane, Kenichi, Suzuki, Akari, Fujio, Keishi, Okamura, Tomohisa, et al; Association Analysis of EGR2 Gene with SLE Susceptibility [abstract]. Arthritis Rheum 2009;60 Suppl 10 :125