Identification of Radiation-Induced Expression Changes in Nonimmortalized Human T Cells
RADIATION RESEARCH
Authors: Pogosova-Agadjanyan, Era L.; Fan, Wenhong; Georges, George E.; Schwartz, Jeffrey L.; Kepler, Crystal M.; Lee, Hana; Suchanek, Amanda L.; Cronk, Michelle R.; Brumbaugh, Ariel; Engel, Julia H.; Yukawa, Michi; Zhao, Lue P.; Heimfeld, Shelly; Stirewalt, Derek L.
Abstract
In the event of a radiation accident or attack, it will be imperative to quickly assess the amount of radiation exposure to accurately triage victims for appropriate care. RNA-based radiation dosimetry assays offer the potential to rapidly screen thousands of individuals in an efficient and cost-effective manner. However, prior to the development of these assays, it will be critical to identify those genes that will be most useful to delineate different radiation doses. Using global expression profiling, we examined expression changes in nonimmortalized T cells across a wide range of doses (0.15-12 Gy). Because many radiation responses are highly dependent on time, expression changes were examined at three different times (3, 8, and 24 h). Analyses identified 61, 512 and 1310 genes with significant linear dose-dependent expression changes at 3, 8 and 24 h, respectively. Using a stepwise regression procedure, a model was developed to estimate in vitro radiation exposures using the expression of three genes (CDKN1A, PSRC1 and TNFSF4) and validated in an independent test set with 86% accuracy. These findings suggest that RNA-based expression assays for a small subset of genes can be employed to develop clinical biodosimetry assays to be used in assessments of radiation exposure and toxicity. (C) 2011 by Radiation Research Society
Associations between TNFAIP3 gene polymorphisms and systemic lupus erythematosus risk: an updated meta-analysis
HLA
Authors: Zhang, M. -Y.; Yang, X. -K.; Pan, H. -F.; Ye, D. -Q.
Abstract
In order to determine whether tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene polymorphisms confers susceptibility to systemic lupus erythematosus (SLE) in ethnically different populations. A meta-analysis was conducted to examine the association between TNFAIP3 polymorphisms and susceptibility to SLE. A systematic literature search was conducted to identify all relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the association. A total of 23 studies from 20 articles, involving 18,501 patients with SLE and 30,435 healthy controls were included in this meta-analysis. Overall, we found significant association between SLE and the TNFAIP3 rs2230926, rs5029937, rs5029939, and rs3757173 polymorphisms (all P<0.001). Stratification by ethnicity indicated that rs5029939 polymorphism was associated with SLE in Europeans, while rs2230926, rs5029937, and rs3757173 polymorphisms were associated with SLE both in Europeans and Asians (all P<0.001). The results of our meta-analysis suggest that TNFAIP3 (rs2230926, rs5029937, rs5029939, and rs3757173) polymorphisms are associated with susceptibility to SLE.