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Allele-specific quantification of TNFA transcripts in rheumatoid arthritis
B M Brinkman1, T W Huizinga, F C Breedveld
1Department of Rheumatology, University Hospital Leiden, The Netherlands.
Human Genetics
|June 1, 1996
Summary
This study investigated tumor necrosis factor alpha (TNFA) gene expression in rheumatoid arthritis (RA). Results show no evidence that distinct TNFA alleles contribute to RA susceptibility through differential mRNA expression.
Area of Science:
- Immunology
- Genetics
- Rheumatology
Background:
- Tumor necrosis factor alpha (TNFA) is implicated in rheumatoid arthritis (RA) pathogenesis.
- Interindividual variation in TNFA expression suggests distinct functional alleles may influence RA susceptibility.
Purpose of the Study:
- To investigate whether differential TNFA gene expression exists in RA patients.
- To determine the contribution of TNFA alleles to total TNFA mRNA in RA patients and healthy individuals.
Main Methods:
- Analyzed allelic TNFA mRNA expression in peripheral blood mononuclear cells and synovial biopsy samples from RA patients.
- Utilized a C-insertion polymorphism in the 5' untranslated region of the TNFA gene to differentiate allelic contributions in heterozygous individuals.
Main Results:
- No significant variation was found in mRNA transcribed from each TNFA allele under in vitro and physiological stimulation conditions in RA patients.
- The study did not detect differences in TNFA mRNA levels attributable to specific alleles.
Conclusions:
- The findings do not support a role for transcriptionally distinct TNFA alleles in rheumatoid arthritis susceptibility.
- Differential TNFA gene expression at the mRNA level does not appear to be a major factor in RA pathogenesis.