Reference
Complete the bibliographic reference for the article according to AJE format.

Oguma T, et al. Role of Prostanoid DP Receptor Variants in Susceptibility to Asthma. NEJM. 2004; 351:1752-63.

Category of HuGE information
Specify the types of information (from the list below) available in the article:

1. Prevalence of gene variant
2. Gene-disease association
3. Gene-environment interaction
4. Gene-gene interaction
5. Genetic test evaluation/monitoring

2. Gene-disease association

Study hypotheses or purpose
The authors study hypotheses or main purpose for conducting the study

Gene(s)
Identification of the following:

1. Gene name
2. Chromosome location
3. Gene product/function
4. Alleles
5. OMIM #
6. GDPInfo link

1. Gene name: PTGDR
2. Chromosome location: 14q22.1
3. Gene product/function: Encodes a heptahelical transmembrane G-protein-coupled receptor
4. Alleles: T-549C located in the promoter, C-441T located in the promoter, T-197C located in the promoter, G+1044A in linkage disequilibrium with T-197C
5. OMIM #: 604687 ²
6. Go to GDPInfo Genes A-Z result

N/A

Health outcome(s)
Identification of the major health outcome(s) studied

Asthma according to the case definition set by the American Thoracic Society

1. Case-control
2. Cohort 
3. Cross-sectional
4. Descriptive or case series
5. Clinical trial
6. Population screening

1. Disease case definition
2. Exclusion criteria
3. Gender
4. Race/ethnicity
5. Age
6. Time period
7. Geographic location
8. Number of participants

1. Disease case definition: Asthma
2. Exclusion criteria: White and African American cases were selected from 20 U.S. centers for a drug-treatment trial
3. Gender: M 51% and F 49%
4. Race/ethnicity: White and African American
5. Age: Whites 34.0 +,- 13.9; Blacks 33.0 +,- 11.8
6. Time period: not specified
7. Geographic location: not specified
8. Number of participants: 518 White cases; 80 Black cases

1. Control selection criteria
2. Matching variables
3. Exclusion criteria
4. Gender
5. Race/ethnicity
6. Age
7. Time period
8. Geographic location
9. Number of participants

1. Control selection criteria: Selected from U.S. Army
2. Matching variables: racially matched
3. Exclusion criteria: controls could not have any history of asthma, atopy, or significant medical illness
4. Gender: M 57% and F 43%
5. Race/ethnicity: White and African American
6. Age: Whites 26.0 +,- 8.1; Blacks 23.5 +,- 5.3
7. Time period: not specified
8. Geographic location: not specified
9. Number of participants: 175 White controls; 45 Black controls

Cohort definition
For study designs 2, 3, and 6, define the following if available:

1. Cohort selection criteria
2. Exclusion criteria
3. Gender
4. Race/ethnicity
5. Age
6. Time period
7. Geographic location
8. Number of participants (% of total eligible)

N/A

1. Environmental factor
2. Exposure assessment
3. Exposure definition
4. Number of participants with exposure data (% of total eligible)

N/A

1. Gene
2. DNA source
3. Methodology
4. Number of participants genotyped (% of total eligible) 

1. Gene: PTGDR
2. DNA source: Whole blood
3. Genotyping method: PTGDR constructs of 1102bp were created using PCR amplification of genomic DNA. Fragment lengths were determined using restriction-fragment-length polymorphism analysis.
4. Number of participants genotyped: all people in study, 818

Analysis
Comment on the analysis carried out by the author(s), e.g. matching, modeling or statistical tests used. Were the analyses appropriate?

• The researchers assessed the SNPs for Hardy-Weinberg equilibrium.
• The effects of multiple covariates on the continuous and dichotomous outcomes were analyzed using generalized linear models.
• Sex and age were analyzed as potential confounders

The analyses were appropriate to assess whether functional variants of the PTGDR gene were associated with an increased risk of asthma.

1. Prevalence of gene variant
2. Gene-disease association
3. Gene-environment interaction
4. Gene-gene interaction
5. Genetic test evaluation/monitoring

1. Within two genetically distinct populations, 35% of the chromosomes contained genetic variants that influence the expression of PTGDR

2. Within the white population, people with at least one copy of the TCT haplotype were less likely to express asthma (OR, 0.55; 95% CI, 0.38-.80; P=0.002). There were similar findings in the black population (OR, 0.32; 95% CI, 0.12-0.89; P=0.03).

The researchers showed that variants of the PTGDR gene are associated with both an increased and decreased risk of asthma in both white and black populations. Particularly, people with at least one copy of the TCT haplotype had a lower risk of asthma.

Selection bias could have occurred when the controls were chosen from the U.S. Army. Future studies should make better choices for their control group. The discovery of functional gene variants of the PTGDR gene and their association to asthma is an important step to developing a risk model for asthma. One of the major strengths of this study is the biological plausibility of the association of PTGDR with asthma ³. The researchers suggest a large scale study, population based study to assess the association of PTGDR with asthma, and if the results are reproduced, the PTGDR gene may be a target of future therapies.

1. Oguma T, Palmer LJ, Birben E, Sonna LA, Asano K, Lilly CM. Role of prostanoid DP receptor variants in susceptibility to asthma. New England Journal of Medicine 2004;351:1752-1763.
2. Entrez Gene. PTGDR prostaglandin D2 receptor (DP) [Homo sapiens].
3. Cookson, W., et al. Making Sense of Asthma Genes. New England Journal of Medicine. 2004; 351:1794-1796