Document Detail

Different apoptotic responses of RA synoviocytes depending on different genotypes of the mdm2 SNP T309G.
MedLine Citation:
PMID:  22187011     Owner:  NLM     Status:  Publisher    
Mdm2 is an ubiquitin ligase, which binds p53 and blocks its function as a transcription factor in the pathway of apoptosis. Recently we have showed that the SNP mdm2 T309G has a protective effect of the minor allele in rheumatoid arthritis (RA). However, a functional impact on apoptosis by the different genotypes of the mdm2 SNP has not been investigated. Genomic DNA was obtained from 49 cell lines of synoviocytes derived from 49 patients with RA, and the mdm2 SNP309 was genotyped by polymerase chain reaction and restriction enzyme analysis. Seven cell lines were identified as homozygous for TT (major allele of mdm2 SNP309), and four as homozygous for GG (minor allele). All 11 cell lines were stimulated with 5 ng/ml of TNF alpha and 2.5 ng/ml of Il-1beta. After staining with propidium iodide (25 µg/ml) DNA fluorescence was measured with FACS; the rate of apoptosis was defined as the percentage of cells with a sub-2n DNA content (= less than haploid DNA-content). The cell-lines genotyped with mdm2 SNP 309TT showed a significantly different apoptosis rate in percent compared with GG for both conditions with stimulation (19.4 ± 3.6 vs. 26.9 ± 1.8; P = 0.02) and without stimulation by TNF alpha and Il-1beta (27.4 ± 8.8 vs. 43.9 ± 2.4; P = 0.0002). In the cell culture in vitro model RA synoviocytes homozygous for mdm2 SNP 309GG had a higher apoptotic activity compared to TT, possibly identifying a protective effect of the minor allele.
Kristina Heyne; Judith Huwer; Vincent Zimmer; Michael Pfreundschuh; Jasmin Teresa Ney; Gunter Assmann
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-21
Journal Detail:
Title:  Apoptosis : an international journal on programmed cell death     Volume:  -     ISSN:  1573-675X     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9712129     Medline TA:  Apoptosis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Internal Medicine I and José-Carreras-Research Center, University of Saarland Medical School, 66421, Homburg/Saar, Germany.
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