Genetic variation in the TNFA promoter region and TNFA gene expression in subjects with asthma

Bridgette L. Jones, Belinda K. Graham, Amanda K. Riffel, Hongying Dai, Lanny J. Rosenwasser, Carrie A. Vyhlidal

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objective. Asthma is a chronic disease that affects millions of people. Messenger RNA (mRNA) expression of specific inflammatory markers has been associated with asthma and corticosteroid response. Tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine, has been shown to have increased expression in airways of asthmatics and may be related to corticosteroid sensitivity. The purpose of this study was to determine how genetic variants within the promoter region of the TNFA gene differ between subjects with asthma and controls. We also investigated how genetic variation affects gene expression. Methods. We enrolled 94 subjects between 5 to 54 years of age who met the inclusion and exclusion criteria. TNFA mRNA expression was determined by qRT-PCR on total RNA isolated from the buccal mucosa. Genotyping was performed for TNFA-1031T/C, -857C/T, and -308G/A on genomic DNA isolated from blood with commercially available assays. Gene expression was log-2 transformed and corrected with 2 normalization genes. General linear model, Chi-square test, Fisher's exact test, and Cochran-Mantel-Haenszel test were performed with p < .05. Results. The TNFA-857C/T polymorphism is associated with asthma in this cohort. The TNFA-857 T allele is underrepresented in pediatric subjects with asthma relative to those without asthma (3% and 29% of individuals, respectively, p = .01). Furthermore, a TNFA haplotype combination containing -1031T/-857C/-308G and -1031T/-857T/-308G is associated with lower expression of TNF-α mRNA (p = .01) in pediatric subjects. Conclusions. Presence of the TNFA-857T allele may be protective in the development of asthma and a haplotype combination that contains the TNFA-857T allele is associated with TNFA expression.

Original languageEnglish (US)
Pages (from-to)541-547
Number of pages7
JournalJournal of Asthma
Volume50
Issue number6
DOIs
StatePublished - Aug 1 2013

Fingerprint

Genetic Promoter Regions
Asthma
Gene Expression
Alleles
Messenger RNA
Haplotypes
Adrenal Cortex Hormones
Tumor Necrosis Factor-alpha
Pediatrics
Mouth Mucosa
Chi-Square Distribution
Genes
Linear Models
Chronic Disease
RNA
Cytokines
Polymerase Chain Reaction
DNA

Keywords

  • Biomarker
  • Cytokine
  • Gene expression
  • Inflammatory markers
  • Polymorphisms

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Immunology and Allergy
  • Pulmonary and Respiratory Medicine

Cite this

Jones, B. L., Graham, B. K., Riffel, A. K., Dai, H., Rosenwasser, L. J., & Vyhlidal, C. A. (2013). Genetic variation in the TNFA promoter region and TNFA gene expression in subjects with asthma. Journal of Asthma, 50(6), 541-547. https://doi.org/10.3109/02770903.2013.792350

Genetic variation in the TNFA promoter region and TNFA gene expression in subjects with asthma. / Jones, Bridgette L.; Graham, Belinda K.; Riffel, Amanda K.; Dai, Hongying; Rosenwasser, Lanny J.; Vyhlidal, Carrie A.

In: Journal of Asthma, Vol. 50, No. 6, 01.08.2013, p. 541-547.

Research output: Contribution to journalArticle

Jones, Bridgette L. ; Graham, Belinda K. ; Riffel, Amanda K. ; Dai, Hongying ; Rosenwasser, Lanny J. ; Vyhlidal, Carrie A. / Genetic variation in the TNFA promoter region and TNFA gene expression in subjects with asthma. In: Journal of Asthma. 2013 ; Vol. 50, No. 6. pp. 541-547.
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abstract = "Objective. Asthma is a chronic disease that affects millions of people. Messenger RNA (mRNA) expression of specific inflammatory markers has been associated with asthma and corticosteroid response. Tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine, has been shown to have increased expression in airways of asthmatics and may be related to corticosteroid sensitivity. The purpose of this study was to determine how genetic variants within the promoter region of the TNFA gene differ between subjects with asthma and controls. We also investigated how genetic variation affects gene expression. Methods. We enrolled 94 subjects between 5 to 54 years of age who met the inclusion and exclusion criteria. TNFA mRNA expression was determined by qRT-PCR on total RNA isolated from the buccal mucosa. Genotyping was performed for TNFA-1031T/C, -857C/T, and -308G/A on genomic DNA isolated from blood with commercially available assays. Gene expression was log-2 transformed and corrected with 2 normalization genes. General linear model, Chi-square test, Fisher's exact test, and Cochran-Mantel-Haenszel test were performed with p < .05. Results. The TNFA-857C/T polymorphism is associated with asthma in this cohort. The TNFA-857 T allele is underrepresented in pediatric subjects with asthma relative to those without asthma (3{\%} and 29{\%} of individuals, respectively, p = .01). Furthermore, a TNFA haplotype combination containing -1031T/-857C/-308G and -1031T/-857T/-308G is associated with lower expression of TNF-α mRNA (p = .01) in pediatric subjects. Conclusions. Presence of the TNFA-857T allele may be protective in the development of asthma and a haplotype combination that contains the TNFA-857T allele is associated with TNFA expression.",
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AU - Jones, Bridgette L.

AU - Graham, Belinda K.

AU - Riffel, Amanda K.

AU - Dai, Hongying

AU - Rosenwasser, Lanny J.

AU - Vyhlidal, Carrie A.

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AB - Objective. Asthma is a chronic disease that affects millions of people. Messenger RNA (mRNA) expression of specific inflammatory markers has been associated with asthma and corticosteroid response. Tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine, has been shown to have increased expression in airways of asthmatics and may be related to corticosteroid sensitivity. The purpose of this study was to determine how genetic variants within the promoter region of the TNFA gene differ between subjects with asthma and controls. We also investigated how genetic variation affects gene expression. Methods. We enrolled 94 subjects between 5 to 54 years of age who met the inclusion and exclusion criteria. TNFA mRNA expression was determined by qRT-PCR on total RNA isolated from the buccal mucosa. Genotyping was performed for TNFA-1031T/C, -857C/T, and -308G/A on genomic DNA isolated from blood with commercially available assays. Gene expression was log-2 transformed and corrected with 2 normalization genes. General linear model, Chi-square test, Fisher's exact test, and Cochran-Mantel-Haenszel test were performed with p < .05. Results. The TNFA-857C/T polymorphism is associated with asthma in this cohort. The TNFA-857 T allele is underrepresented in pediatric subjects with asthma relative to those without asthma (3% and 29% of individuals, respectively, p = .01). Furthermore, a TNFA haplotype combination containing -1031T/-857C/-308G and -1031T/-857T/-308G is associated with lower expression of TNF-α mRNA (p = .01) in pediatric subjects. Conclusions. Presence of the TNFA-857T allele may be protective in the development of asthma and a haplotype combination that contains the TNFA-857T allele is associated with TNFA expression.

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KW - Polymorphisms

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