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. 1999 Nov;58(Suppl 1):I20–I26. doi: 10.1136/ard.58.2008.i20

Tumour necrosis factor gene polymorphisms as severity markers in rheumatoid arthritis

C Verweij
PMCID: PMC1766583  PMID: 10577969

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Figure 1  .

Figure 1  

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Schematic representation of the location of the TNF gene within the major histocompatibility complex. The middle row represents the intron/exon organisation of the TNF and LT genes. The arrows indicate the transcriptional orientation of the TNF and LT genes. At the bottom the 5' region of the gene including the transcription initiation site is depicted. The position of the SNPs within this part of the gene is indicated.

Figure 2  .

Figure 2  

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Joint damage in relation to the TNF +489 and −238 polymorphism in a prospective cohort of RA patients. The median radiographic damage score expressed as modified Sharp score for radiographs of hands and feet for the TNF +489 GG and GA patients (panel A) and the TNF −238 GG and GA patients (panel B) is presented. Modified Sharp scores at onset (t=0), at 3, 6 and 12 years is depicted.

Figure 3  .

Figure 3  

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Schematic representation of the human TNF locus and the TNF promoter/reportergene constructs used to study the functional relevance of the −376, −308 and −238 gene variants. In the right panel the results of the transfections are shown. Presented are the results from at least three independent transfections with three different batches of DNA. Reportergene expression is expressed as the relative activity of the plasmid with the highest activity (100%) reached at after stimulation in each experiment. Relative reportergene expression levels were averaged (SD) and plotted in histograms. Jurkat cells were unstimulated (open bars) or stimulated for 24 hours with anti-CD3 (0.5 µg/ml) and anti-CD28 (5 µg/ml) (filled bars). Raji cells were unstimulated (open bars) or stimulated for 24 hours with PMA (50 ng/ml) filled bars. U937 and Mono Mac 6 were unstimulated (open bars) or stimulated (filled bars) for four hours with LPS (1 µg/ml)/PMA (10 ng/ml) and LPS, respectively. ND = not determined.

Figure 4  .

Figure 4  

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Analysis of the relative contribution of the two +489 alleles in the total TNF precursor mRNA synthesis.Upper panel gives a schematic representation of the genotype of a person heterozygous for the +489 polymorphism. The G at position +489 creates a Tai1 restriction site that is not cleavable in the A allele. PBMC of heterozygous subjects are stimulated with LPS (10 ng/ml) for four hours and RNA is isolated. RNA is reversed transcribed and PCR amplified by two primers spanning the TNF region of interest. Precursor TNF RT-PCR product is digested with Tai to discriminate between the relative contribution of the respective alleles in total TNF precursor production. On the gel results are shown from three people tested. Lane 1; Analysis on genomic DNA from one of the subjects as control (theoretically 1:1), lane 2-4: results from cells stimulated with LPS 10 ng/ml. The A indicates the fragment representing the noncleavable +489A fraction of the transcript. The G the cleavable +489G fraction.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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