PMID- 23557460
OWN - NLM
STAT- MEDLINE
DCOM- 20130916
LR  - 20221207
IS  - 1532-4303 (Electronic)
IS  - 0277-0903 (Linking)
VI  - 50
IP  - 6
DP  - 2013 Aug
TI  - Genetic variation in the TNFA promoter region and TNFA gene expression in 
      subjects with asthma.
PG  - 541-7
LID - 10.3109/02770903.2013.792350 [doi]
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-alpha (TNF-alpha), 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-alpha 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.
FAU - Jones, Bridgette L
AU  - Jones BL
AD  - Children's Mercy Hospital, Kansas City, MO, USA. bljones@cmh.edu
FAU - Graham, Belinda K
AU  - Graham BK
FAU - Riffel, Amanda K
AU  - Riffel AK
FAU - Dai, Hongying
AU  - Dai H
FAU - Rosenwasser, Lanny J
AU  - Rosenwasser LJ
FAU - Vyhlidal, Carrie A
AU  - Vyhlidal CA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130513
PL  - England
TA  - J Asthma
JT  - The Journal of asthma : official journal of the Association for the Care of 
      Asthma
JID - 8106454
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Black or African American/*genetics
MH  - Asthma/*genetics
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Gene Expression
MH  - Genetic Variation
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mouth Mucosa/metabolism
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/metabolism
MH  - Tumor Necrosis Factor-alpha/*genetics
MH  - White People/genetics
MH  - Young Adult
EDAT- 2013/04/06 06:00
MHDA- 2013/09/17 06:00
CRDT- 2013/04/06 06:00
PHST- 2013/04/06 06:00 [entrez]
PHST- 2013/04/06 06:00 [pubmed]
PHST- 2013/09/17 06:00 [medline]
AID - 10.3109/02770903.2013.792350 [doi]
PST - ppublish
SO  - J Asthma. 2013 Aug;50(6):541-7. doi: 10.3109/02770903.2013.792350. Epub 2013 May 
      13.