Variant "NOS1:AAT repeat polymorphism in intron 20 of the NOS1"
Search results: 2 records
Variant information
Gene:
NOS1 
Variant:
NOS1:AAT repeat polymorphism in intron 20 of the NOS1 
dbSNP ID:
no data 
GWAS trait:
no data 
Modifier statisitcs
Record:
2 
Disorder:
1 
Reference:
2 
Effect type:
Pleiotropy(2)  
Modifier effect:
Altered Pseudomonas aeruginosa colonization rate(1) ,Altered variability of FENO and P. aeruginosa colonization(1)  
Details：
  • Target disease:
    Cystic fibrosis (DOID_1485)
    Effect type:
    Pleiotropy 
    Modifier effect:
    Altered variability of FENO and P. aeruginosa colonization 
    Evidence:
    4.0 +/- 0.8 [mean +/- sem] ppb versus 6.4 +/- 0.9 ppb, P=0.027 
    Effect:
    The NOS1 gene is not only associated with the variability of FENO, but also with P. aeruginosa colonization of airways in CF patients.
    Reference:
    PMID11112133
    Title:
    Airway nitric oxide levels in cystic fibrosis patients are related to a polymorphism in the neuronal nitric oxide synthase gene.
    Species studied:
    Human
    Abstract:
    Patients with cystic fibrosis (CF) have decreased concentrations of expired nitric oxide (FENO) as compared with healthy individuals. A number of factors, including viscous mucus as a diffusion barrier for airway NO, consumption of NO by bacterial enzymes, and decreased NO production have been hypothesized to account for these low levels of FENO. We examined the relationship between the size of an AAT repeat polymorphism in intron 20 of the NOS1 gene and FENO in 75 patients with CF. Mean FENO was significantly (p = 0.027) lower in CF patients who harbored two alleles with a high number of repeats (>/= 12) than in those who harbored alleles with fewer repeats at this locus (4.0 +/- 0.8 [mean +/- SEM] ppb versus 6.4 +/- 0.9 ppb). Colonization of the airways with Pseudomonas aeruginosa was significantly (p = 0.0358) more common in CF patients with high numbers of AAT repeats in the NOS1 gene. Significant differences between NOS1 genotypes were also observed among patients homozygous for the cystic fibrosis transmembrane regulator delta F508 mutation for FENO (2.3 +/- 0.4 ppb versus 5.3 +/- 0.7 ppb, p = 0.0006), and this was also true for colonization of the airways with P. aeruginosa (p = 0.0147) and Aspergillus fumigatus (p = 0.0221). These data provide evidence that the NOS1 gene is not only associated with the variability of FENO, but also with P. aeruginosa colonization of airways in CF patients.
  • Target disease:
    Cystic fibrosis (DOID_1485)
    Effect type:
    Pleiotropy 
    Modifier effect:
    Altered Pseudomonas aeruginosa colonization rate 
    Evidence:
    From review article 
    Effect:
    Higher Pseudomonas aeruginosa colonization rate with both alleles >12 repeats
    Reference:
    PMID16124861
    Title:
    Modifier genetics: cystic fibrosis.
    Species studied:
    Human
    Abstract:
    Cystic fibrosis (CF) is the most common lethal autosomal recessive disorder in the Caucasian population, affecting about 30,000 individuals in the United States. The gene responsible for CF, the CF transmembrane conductance regulator (CFTR), was identified 15 years ago. Substantial variation in the many aspects of the CF phenotype among individuals with the same CFTR genotype demonstrates that factors independent of CFTR exert considerable influence on outcome in CF. To date, the majority of published studies investigating the cause of disease variability in CF report associations between candidate genes and some aspect of the CF phenotype. However, a definitive modifier gene for CF remains to be identified. Despite the challenges posed by searches for modifier effects, studies of affected twins and siblings indicate that genetic factors play a substantial role in intestinal manifestations. Identifying the factors contributing to variation in pulmonary disease, the primary cause of mortality, remains a challenge for CF research.