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Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Tumour necrosis factor gene polymorphisms and childhood wheezing
H Bilolikar1, A R Nam, M Rosenthal
1Dept of Paediatric Respiratory Medicine, Royal BromptonHospital, Sydney Street, London SW3 6NP, UK.
Genetic variations in tumour necrosis factor (TNF)-alpha and lymphotoxin-alpha influence childhood asthma and wheezing risk. Specific gene polymorphisms identify infants at higher risk for these respiratory conditions.
Area of Science:
- Immunogenetics
- Pediatric Respiratory Medicine
- Molecular Biology
Background:
- Tumour necrosis factor (TNF)-alpha is implicated in childhood wheezing.
- Genetic factors, specifically single nucleotide gene polymorphisms (SNPs), may predispose individuals to increased TNF-alpha production.
- Understanding these genetic links is crucial for identifying at-risk populations.
Purpose of the Study:
- To investigate the association between TNF-alpha-308G/A and lymphotoxin (LT)-alpha+252G/A gene polymorphisms and the risk of childhood asthma and infant wheezing.
- To analyze the impact of specific TNF-alpha and LT-alpha genotypes and haplotypes on disease susceptibility.
- To explore the relationship between these polymorphisms and nasal TNF-alpha levels in infants with wheezing.
Main Methods:
- Comparative analysis of TNF-alpha-308G/A and LT-alpha+252G/A polymorphism frequencies in asthmatic children, wheezy infants, and control groups from the UK.
- Haplotype analysis to determine combined genetic risks and protective effects.
- Measurement of nasal TNF-alpha levels in infants during wheezing episodes, correlated with specific genotypes.
Main Results:
- Significant differences in genotype frequencies for TNF-alpha-308 and LT-alpha+252 polymorphisms were observed compared to controls.
- Specific haplotypes, such as TNF-alpha-308G/LT-alpha+252A and TNF-alpha-308A/LT-alpha+252A, were associated with increased risk for asthma and infant wheezing.
- A protective effect was noted for the TNF-alpha-308G/LT-alpha+252G/TNF-alpha-308G, LT-alpha+252A haplotype.
- Nasal TNF-alpha levels were influenced by TNF-alpha-308/LT-alpha+252 genotype combinations, with lower levels found in the presence of TNF-alpha-308A alleles.
Conclusions:
- Genetic variations in TNF-alpha and LT-alpha play a significant role in the risk of childhood wheezing and asthma.
- Haplotype analysis provides valuable insights into the complex genetic underpinnings of these conditions.
- These findings can inform early intervention strategies by identifying high-risk infants for targeted monitoring and management.
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