Gene "TLR5"
Found 2 records
Gene information
Gene symbol:
TLR5
See related:
Ensembl: ENSG00000187554, Gene ID: 7100
Additive variants :
Undetected
Genetic interaction partners
No data
Modifier statisitcs
Record:
Disorder:
Vriant:
Reference:
Effect type:
Expressivity(1) ,Pleiotropy(1)  
Modifier effect:
Altered phenotype(1) ,Anti-inflammatory target(1)  
Details:
  • Gene:
    Genomic location:
    chr1:223285200
    dbSNP ID:
    Alias:
    TLR5:rs5744168
    Target disease:
    Cystic fibrosis(DOID_1485)
    Effect type:
    Expressivity 
    Modifier effect:
    Anti-inflammatory target 
    Evidence:
    P<0.0001 
    Effect:
    Adults with CF carrying the TLR5 premature stop codon (CT or TT genotype) had a higher body mass index than did CF patients homozygous for the fully functional allele (CC genotype)
    Reference:
    Title:
    TLR5 as an anti-inflammatory target and modifier gene in cystic fibrosis.
    Species studied:
    Human
    Abstract:
    New treatments are needed to improve the health of people with cystic fibrosis (CF). Reducing lung-damaging inflammation is likely to be beneficial, but specific anti-inflammatory targets have not been identified. By combining cellular immunology with a population-based genetic modifier study, we examined TLR5 as an anti-inflammatory target and modifier gene in CF. Using two pairs of human CF and control airway epithelial cells, we demonstrated that the TLR5-flagellin interaction is a major mediator of inflammation following exposure to Pseudomonas aeruginosa. To validate TLR5 as an anti-inflammatory target, we analyzed the disease modifying effects of the TLR5 c.1174C>T single nucleotide polymorphism (rs5744168) in a large cohort of CF patients (n = 2219). rs5744168 encodes a premature stop codon and the T allele is associated with a 45.5-76.3% reduction in flagellin responsiveness (p < 0.0001). To test the hypothesis that reduced TLR5 responsiveness would be associated with improved health in CF patients, we examined the relationship between rs5744168 and two clinical phenotypes: lung function and body weight. Adults with CF carrying the TLR5 premature stop codon (CT or TT genotype) had a higher body mass index than did CF patients homozygous for the fully functional allele (CC genotype) (p = 0.044); however, similar improvements in lung function associated with the T allele were not statistically significant. Although follow-up studies are needed to confirm the impact of TLR5 on nutritional status, this translational research provides evidence that genetic variation in TLR5 resulting in reduced flagellin responsiveness is associated with improved health indicators in adults with CF.
  • Gene:
    Genomic location:
    chr1:223285200
    dbSNP ID:
    Alias:
    TLR5:rs5744168
    Target disease:
    Cystic fibrosis(DOID_1485)
    Effect type:
    Pleiotropy 
    Modifier effect:
    Altered phenotype 
    Evidence:
    From review article 
    Effect:
    Lung disease
    Reference:
    Title:
    Disease-modifying genes and monogenic disorders: experience in cystic fibrosis.
    Species studied:
    Human
    Abstract:
    The mechanisms responsible for the determination of phenotypes are still not well understood; however, it has become apparent that modifier genes must play a considerable role in the phenotypic heterogeneity of Mendelian disorders. Significant advances in genetic technologies and molecular medicine allow huge amounts of information to be generated from individual samples within a reasonable time frame. This review focuses on the role of modifier genes using the example of cystic fibrosis, the most common lethal autosomal recessive disorder in the white population, and discusses the advantages and limitations of candidate gene approaches versus genome-wide association studies. Moreover, the implications of modifier gene research for other monogenic disorders, as well as its significance for diagnostic, prognostic, and therapeutic approaches are summarized. Increasing insight into modifying mechanisms opens up new perspectives, dispelling the idea of genetic disorders being caused by one single gene.