|
|
Reference
Complete the bibliographic reference for the article according to AJE format.
|
Silverman, Eric S, et al. Transforming growth factor-beta1 promoter polymorphism C-509T is associated with asthma. AJRCCM 2003 November; 169:214-219s. |
Category of HuGE information
Specify the types of information (from the list below) available in the article:
- Prevalence of gene variant
- Gene-disease association
- Gene-environment interaction
- Gene-gene interaction
- Genetic test evaluation/monitoring
|
2. Gene-disease association |
Study hypotheses or purpose
The authors study hypotheses or main purpose for conducting the study
|
Hypothesis: The C-509T polymorphism in the TGF beta 1 gene promoter is associated with asthma in a large population of well characterized cases with asthma compared with genetically matched controls.
|
Gene(s)
Identification of the following:
- Gene name
- Chromosome location
- Gene product/function
- Alleles
- OMIM #
|
- Gene name: TGFB1
- Chromosome location: 19q13.1-q13.3
- Gene product/function: multiple function peptide involved in the suppression of cell proliferation, inflammatory immune response and blood vessel growth and deposition of extracellular matrix
- Alleles: C-509T, which is in the promoter region, so is non-coding.
- OMIM #: 190180
|
Environmental factor(s)
Identification of the major environmental factors studied (infectious, chemical, physical, nutritional, and behavioral)
|
None |
Health outcome(s)
Identification of the major health outcome(s) studied
|
Case or control status for asthma |
Study design
Specification of the type of study design(s)
- Case-control
- Cohort
- Cross-sectional
- Descriptive or case series
- Clinical trial
- Population screening
|
1. Case-control Study |
Case definition
For study designs 1, 4, and 5, define the following if available:
- Disease case definition
- Exclusion criteria
- Gender
- Race/ethnicity
- Age
- Time period
- Geographic location
- Number of participants
|
- Disease case definition: Moderate to severe asthma as defined by the American Thoracic Society (compatible history and reversibility of airflow by beta agonist or methacholine sensitivity testing with spirometry à 40-85 % FEV1).
- Exclusion criteria: smoker, less than 18 years or more than 45 years of age or having significant co-morbid condition
- Gender: males and females
- Race/ethnicity: white (Caucasian) only
- Age: mean age 33.7 years for cases (standard deviation 13.7)
- Time period: ‘not specified’
- Geographic location: United States
- Number of participants: 527
|
Control definition
For study design 1, define the following if available:
- Control selection criteria
- Matching variables
- Exclusion criteria
- Gender
- Race/ethnicity
- Age
- Time period
- Geographic location
- Number of participants
|
- Control selection criteria: Without asthma, selected from and characterized in the Environmental Medicine Genome Bank (EMGB), which includes US army recruits from across the country in basic training; assessed for sex, age, history of asthma, or exercise induced bronchospasm, spirometry and total serum IgE.
- Matching variables: Genetic matching was done on 311of the 527cases and 170 of the controls at 49 unlinked markers(1).
- Exclusion criteria: Asthma, using medications for asthma regardless of symptoms, reliable diagnosis of obstructive airway disease at any age Gender: males and females
- Race/ethnicity: white (Caucasian) only
- Age: 25.7 years for controls (Standard deviation 7.6)
- Time period: ‘not specified’
- Geographic location: United States
- Number of participants: 170
|
Cohort definition
For study designs 2, 3, and 6, define the following if available:
- Cohort selection criteria
- Exclusion criteria
- Gender
- Race/ethnicity
- Age
- Time period
- Geographic location
- Number of participants
|
N/A |
Assessment of environment factors
For studies that include gene-environment interactions, define the following, if available:
- Environmental factor
- Exposure assessment
- Exposure definition
- Number of participants with exposure data (% of total eligible)
|
N/A
|
Genotyping
Specify the following:
- Gene
- DNA source
- Methodology
- Number of participants genotyped (% of total eligible)
|
- Gene: TGFB1 promoter C-509T
- DNA source: peripheral blood
- Methodology: Restriction fragment length polymorphism analysis, described in online supplement to article Silverman et al (2)(a)
- Number of participants genotyped: 697 (100% of total eligible)
|
Results
Describe the major results under each of the following HuGE categories. Include tables when data are provided:
- Prevalence of gene variant
- Gene-disease association
- Gene-environment interaction
- Gene-gene interaction
- Genetic test evaluation/monitoring
|
Genotype frequency and disease association
T/T |
69
(13.1%) |
11
(6.5%) |
2.5
(1.3-5.1) |
2.98
(1.45-6.25) |
T/C |
246
(46.7%) |
76
(44.7%) |
1.3
(0.9-1.8) |
1.43
(0.96-2.14) |
C/C |
212
(40.2%) |
83
(48.8%) |
ref |
Ref |
|
* UOR - Univariate Odds Ratio
+ Multivariate Odds Ratio (adjusted for age and sex)
|
Conclusion
State the author's overall conclusions from the study |
The authors found a strong positive association between the T allele and the TT genotype of the TGF b 1 promoter gene (C-508) with the diagnosis of asthma among white adults ages 18 to 45 years.
|
Comments
Provide additional insight, including methodologic issues and/or concerns about the study |
Strengths:
Biologically plausible, large number of cases, population stratification addressed using 49 other unlinked markers, “strict” application of asthma case definition, and previously described association. Authors’ assessment of gene function suggests a functional role of the gene polymorphism, adding to the biologic plausibility.
Weaknesses:
The study base of the case and control subjects may not be the same, especially for environmental exposures. No association of genotype with FEV1%, IgE levels or eosinophil count.
Concerns:
The lack of association with the % FEV1, IgE levels and eosinophil count may be related to confounding due to the lack of a “gold standard” case definition for asthma. There are many genes related to the phenotype of asthma.(3); the TGFB1 gene also is involved in many other conditions (lung and non lung) and it may be have limited specificity or sensitivity as a marker for asthma.
|
References
-
Rebecca M. Baron, et al. DNA Sequence Variants in Epithelium-Specific ETS-2 and ETS-3 Are Not Associated with Asthma. Am J Respir Crit Care Med 2002; 166: 927-932,
-
Silverman, Eric S, et al. Transforming growth factor-beta1 promoter polymorphism C-509T is associated with asthma. AJRCCM 2003 November; 169:214-219s. Online supplement
-
Hakonarson H, et al. Allelic frequencies and patterns of single-nucleotide polymorphisms in candidate genes for asthma and atopy in Iceland . Am J Respir Crit Care Med 2001 Dec 1;164(11):2036-44.
|