Prostanoid DP receptor polymorphisms may cause changes in susceptibility to asthma
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《胸》
Clinical Research Fellow, North West Lung Centre, Manchester, UK; cpryspicard@fs1.with.man.ac.uk
Oguma T, Palmer LJ, Birben E, et al. Role of prostanoid DP receptor variants in susceptibility to asthma. N Engl J Med 2004;351:1752–63[Abstract/Free Full Text]
Prostaglandins have been implicated in the pathophysiology of asthma. The prostaglandin receptor is expressed on the surface of airway eosinophils and mast cells. This group has studied the gene for the prostanoid DP receptor (PTGDR) and its relationship with the asthma phenotype.
Screening revealed four new single nucleotide polymorphisms (SNPs) in addition to the two previously reported SNPs in the areas of the gene promoter region that bind transcription factors. The frequencies of the four most common SNPs were determined by restriction fragment length polymorphism (RFLP) analysis in patients with mild to moderate asthma and controls. Genotypic analysis showed an increased risk of asthma associated with the T-549C SNP (odds ratio (OR) >2.0; p<0.05) for white and black ethnic groups. The T allele of the C-441T SNP was significantly more common in white subjects with asthma (OR >1.8; p0.02); this association did not reach significance in the black population. Black patients carrying both the C-441T and T-549C alleles were more likely to have asthma (OR 24.36; p = 0.01). Patients who had at least one copy of the haplotype with low transcriptional efficiency were under-represented in the asthma group (OR 0.32 for blacks, 0.55 for whites; p<0.05). There was no association between any of the SNPs and total IgE.
Certain genetic variants that impair the expression of PTGDR seem to reduce susceptibility to asthma. This study supports the hypothesis that PTGDR is one of a number of genes that determine susceptibility to developing the asthma phenotype.(C Prys-Picard)
Oguma T, Palmer LJ, Birben E, et al. Role of prostanoid DP receptor variants in susceptibility to asthma. N Engl J Med 2004;351:1752–63[Abstract/Free Full Text]
Prostaglandins have been implicated in the pathophysiology of asthma. The prostaglandin receptor is expressed on the surface of airway eosinophils and mast cells. This group has studied the gene for the prostanoid DP receptor (PTGDR) and its relationship with the asthma phenotype.
Screening revealed four new single nucleotide polymorphisms (SNPs) in addition to the two previously reported SNPs in the areas of the gene promoter region that bind transcription factors. The frequencies of the four most common SNPs were determined by restriction fragment length polymorphism (RFLP) analysis in patients with mild to moderate asthma and controls. Genotypic analysis showed an increased risk of asthma associated with the T-549C SNP (odds ratio (OR) >2.0; p<0.05) for white and black ethnic groups. The T allele of the C-441T SNP was significantly more common in white subjects with asthma (OR >1.8; p0.02); this association did not reach significance in the black population. Black patients carrying both the C-441T and T-549C alleles were more likely to have asthma (OR 24.36; p = 0.01). Patients who had at least one copy of the haplotype with low transcriptional efficiency were under-represented in the asthma group (OR 0.32 for blacks, 0.55 for whites; p<0.05). There was no association between any of the SNPs and total IgE.
Certain genetic variants that impair the expression of PTGDR seem to reduce susceptibility to asthma. This study supports the hypothesis that PTGDR is one of a number of genes that determine susceptibility to developing the asthma phenotype.(C Prys-Picard)