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Tumour necrosis factor haplotypes and asthma
1Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Headington, Oxford, UK.
Human Molecular Genetics
|April 1, 1997
Summary
Genetic variations in Tumour Necrosis Factor (TNF) and Lymphotoxin alpha (LT alpha) genes are linked to asthma. Specific TNF and LT alpha polymorphisms were associated with increased asthma prevalence in a general population study.
Area of Science:
- Immunogenetics
- Respiratory Medicine
- Human Genetics
Background:
- Airway inflammation is a key characteristic of asthma.
- Tumour Necrosis Factor (TNF) levels exhibit variation due to polymorphisms in the TNF gene complex and MHC region.
Purpose of the Study:
- To investigate the association between asthma and polymorphisms in the TNF gene complex.
- To examine the role of LT alpha NcoI and TNF-308 polymorphisms in asthma pathogenesis.
Main Methods:
- Analysis of 413 subjects from 88 nuclear families in a general population sample.
- Asthma diagnosis based on questionnaire data.
- Genotyping for LT alpha NcoI and TNF-308 polymorphisms.
Main Results:
- Asthma was significantly more prevalent in subjects with LT alpha NcoI*1 (p=0.005) and TNF-308*2 (p=0.004) alleles.
- The association was linked to the LT alpha NcoI*1/TNF-308*2 haplotype.
- The HLA-DR locus was ruled out as the cause of this association.
Conclusions:
- Genetic factors influencing inflammation, specifically TNF and LT alpha polymorphisms, may play a significant role in asthma development.
- Further research is warranted to elucidate the precise mechanisms linking these genetic variants to asthma pathogenesis.