The early growth response gene 2 (EGR2) is located at chromosome 10q21, one of the susceptibility loci in bipolar disorder (BD). EGR2 is involved in cognitive function, myelination, and signal transduction related to neuregulin-ErbB receptor, Bcl-2 family proteins, and brain-derived neurotrophic factor. This study investigated the genetic association of the EGR2 gene with BD and schizophrenia (SPR) in Korea. In 946 subjects (350 healthy controls, 352 patients with BD, and 244 with SPR), nine single nucleotide polymorphisms (SNPs) in the EGR2 gene region were genotyped. Five SNPs showed nominally significant allelic associations with BD (rs2295814, rs61865882, rs10995315, rs2297488, and rs2297489), and the positive associations of all except rs2297488 remained significant after multiple testing correction. Linkage disequilibrium structure analysis revealed two haplotype blocks. Among the common identified haplotypes (frequency > 5%), 'T-G-A-C-T (block 1)' and 'A-A-G-C (block 2)' haplotypes were over-represented, while 'C-G-G-T-T (block 1)' haplotype was under-represented in BD. In contrast, no significant associations were found with SPR. Although an extended analysis with a larger sample size or independent replication is required, these findings suggest a genetic association of EGR2 with BD. Combined with a plausible biological function of EGR2, the EGR2 gene is a possible susceptibility gene in BD.
Adult ; Bipolar Disorder/*genetics ; Early Growth Response Protein 2/*genetics ; Female ; Genetic Predisposition to Disease/genetics ; Genotype ; Haplotypes/genetics ; Humans ; Korea ; Linkage Disequilibrium/genetics ; Male ; Polymorphism, Single Nucleotide/genetics ; Schizophrenia/genetics

OBJECTIVEThe pEgr-TNFalpha plasmid was constructed to investigate the effect of gene-radiotherapy on melanoma and host immune system.

METHODSpEgr-TNFalpha plasmids were constructed and injected into tumor tissue, 36 hours later, the tumors were given 20 Gy X-ray irradiation. Tumor growth at different timepoints was record and immunologic parameters were detected 15 days later.

RESULTSFrom 3 to 15 d after pEgr-TNFalpha gene-radiotherapy the tumor growth was significantly slower than irradiation or genetherapy alone. NK activity, IL-2, TNFalpha and IL-1beta secretion activities of pEgr-TNFalpha gene-radiotherapy group and pEgr-TNFalpha gene group were higher than those of irradiation alone group significantly.

CONCLUSIONThe anti-tumor effect of pEgr-TNFalpha gene-radiotherapy is better than that of either one applied solely, and it can alleviate the lesion caused by radiation therapy.

Animals ; Combined Modality Therapy ; DNA-Binding Proteins ; genetics ; Early Growth Response Protein 1 ; Female ; Genetic Therapy ; Immediate-Early Proteins ; genetics ; Interleukin-2 ; secretion ; Killer Cells, Natural ; immunology ; Melanoma, Experimental ; immunology ; therapy ; Mice ; Plasmids ; Transcription Factors ; genetics ; Tumor Necrosis Factor-alpha ; genetics

Toxoplasma gondii can modulate host cell gene expression; however, determining gene expression levels in intermediate hosts after T. gondii infection is not known much. We selected 5 genes (ALDH1A2, BEX2, CCL3, EGR2 and PLAU) and compared the mRNA expression levels in the spleen, liver, lung and small intestine of genetically different mice infected with T. gondii. ALDH1A2 mRNA expressions of both mouse strains were markedly increased at day 1-4 postinfection (PI) and then decreased, and its expressions in the spleen and lung were significantly higher in C57BL/6 mice than those of BALB/c mice. BEX2 and CCR3 mRNA expressions of both mouse strains were significantly increased from day 7 PI and peaked at day 15-30 PI (P<0.05), especially high in the spleen liver or small intestine of C57BL/6 mice. EGR2 and PLAU mRNA expressions of both mouse strains were significantly increased after infection, especially high in the spleen and liver. However, their expression patterns were varied depending on the tissue and mouse strain. Taken together, T. gondii-susceptible C57BL/6 mice expressed higher levels of these 5 genes than did T. gondii-resistant BALB/c mice, particularly in the spleen and liver. And ALDH1A2 and PLAU expressions were increased acutely, whereas BEX2, CCL3 and EGR2 expressions were increased lately. Thus, these demonstrate that host genetic factors exert a strong impact on the expression of these 5 genes and their expression patterns were varied depending on the gene or tissue.
Aldehyde Dehydrogenase/*genetics/metabolism ; Animals ; Brain/metabolism/parasitology ; Chemokine CCL3/*genetics/metabolism ; Early Growth Response Protein 2/*genetics/metabolism ; Gene Expression Profiling ; Humans ; Lung/metabolism/parasitology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Nerve Tissue Proteins/*genetics/metabolism ; Organ Specificity ; Spleen/metabolism/virology ; Toxoplasma/*physiology ; Toxoplasmosis/*genetics/metabolism/parasitology ; Urokinase-Type Plasminogen Activator/*genetics/metabolism