RGD Reference Report - Association of TNF haplotypes with asthma, serum IgE levels, and correlation with serum TNF-alpha levels. - Rat Genome Database

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Association of TNF haplotypes with asthma, serum IgE levels, and correlation with serum TNF-alpha levels.

Authors: Sharma, S  Sharma, A  Kumar, S  Sharma, SK  Ghosh, B 
Citation: Sharma S, etal., Am J Respir Cell Mol Biol. 2006 Oct;35(4):488-95. Epub 2006 May 25.
RGD ID: 4143372
Pubmed: PMID:16728705   (View Abstract at PubMed)
DOI: DOI:10.1165/rcmb.2006-0084OC   (Journal Full-text)

Both biochemical and genetic evidence have implicated the genes for TNF-alpha (TNFA) and lymphotoxin-alpha (LTA) in atopic asthma. Here, we report for the first time the association of their genotypes and haplotypes with atopic asthma in Indian populations. We genotyped seven single nucleotide polymorphisms, encompassing the two genes, in patients and control subjects in two independent cohorts. Serum TNF-alpha levels of selected individuals were measured and correlated with genotypes and haplotypes. The A allele of the TNFA-863C > A polymorphism was associated with reduced risk of asthma (P = 0.002 and 0.007 in Cohorts A and B, respectively), reduced TsIgE levels (P = 0.0024 and P = 0.0029 in Cohorts A and B, respectively), and reduced serum TNF-alpha levels (P < 0.05). A marginal association was also observed for LTA_NcoI polymorphism with asthma and TsIgE levels. Furthermore, analysis using HAPLO. STATS showed significant differences in the major haplotype frequencies (> 3%) between patients and control subjects (P = 0.002 and P = 0.006 for Cohorts A and B, respectively). Individually, the haplotype GATCCG was the most frequent in patients (P = 0.0029 and P = 0.0025 for Cohorts A and B, respectively), and was associated with high TsIgE and serum TNF-alpha levels, whereas AACACG was the most frequent in the control subjects (P = 0.0032 and P = 0.022 for Cohorts A and B, respectively), and was associated with low TsIgE and serum TNF-alpha levels. We also report here that the C > A substitution at position -863 of the TNFA influences the binding of nuclear proteins in electrophoretic mobility shift assay experiments. Thus, the TNFA-863C > A polymorphism in the promoter region of TNFA may influence TNF-alpha expression and affect TsIgE levels and susceptibility to asthma.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TNFHumanasthma  IAGP DNA:polymorphism:promoter:c.-863C > A (human)RGD 
TnfRatasthma  ISOTNF (Homo sapiens)DNA:polymorphism:promoter:c.-863C > A (human)RGD 
TnfMouseasthma  ISOTNF (Homo sapiens)DNA:polymorphism:promoter:c.-863C > A (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tnf  (tumor necrosis factor)

Genes (Mus musculus)
Tnf  (tumor necrosis factor)

Genes (Homo sapiens)
TNF  (tumor necrosis factor)


Additional Information