Variant "KRT8:c.409-61T>C"
Search results: 3 records
Variant information
Gene:
KRT8 
Variant:
KRT8:c.409-61T>C 
Alias:
KRT8:rs2035875 
dbSNP ID:
rs2035875  
GWAS trait:
no data 
Modifier statisitcs
Record:
3 
Disorder:
1 
Reference:
2 
Effect type:
Expressivity(3)  
Modifier effect:
Altered severity(2) ,CFTR mediated residual chloride secretion(1)  
Details：
  • Target disease:
    Cystic fibrosis (DOID_1485)
    Effect type:
    Expressivity 
    Modifier effect:
    CFTR mediated residual chloride secretion 
    Evidence:
    Pcorr = 0.0069 
    Effect:
    KRT8, but not KRT18, showed an association with CF disease severity (Pbest = 0.00131; Pcorr = 0.0185) and CFTR mediated residual chloride secretion (Pbest = 0.0004; Pcorr = 0.0069).
    Alias in reference:
    KRT8:c.409-61T>C
    Reference:
    PMID21548936
    Title:
    An association study on contrasting cystic fibrosis endophenotypes recognizes KRT8 but not KRT18 as a modifier of cystic fibrosis disease severity and CFTR mediated residual chloride secretion.
    Species studied:
    Human
    Abstract:
    F508del-CFTR, the most frequent disease-causing mutation among Caucasian cystic fibrosis (CF) patients, has been characterised as a mutant defective in protein folding, processing and trafficking. We have investigated the two neighbouring cytokeratin genes KRT8 and KRT18 in a candidate gene approach to ask whether variants in KRT8 and/or KRT18 modify the impaired ion conductance known as the CF basic defect, and whether they are associated with correct trafficking of mutant CFTR and disease severity of CF.
  • Target disease:
    Cystic fibrosis (DOID_1485)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered severity 
    Evidence:
    Pcorr= 0.0185 
    Effect:
    KRT8, but not KRT18, showed an association with CF disease severity (Pbest = 0.00131; Pcorr = 0.0185) and CFTR mediated residual chloride secretion (Pbest = 0.0004; Pcorr = 0.0069).
    Alias in reference:
    KRT8:c.409-61T>C
    Reference:
    PMID21548936
    Title:
    An association study on contrasting cystic fibrosis endophenotypes recognizes KRT8 but not KRT18 as a modifier of cystic fibrosis disease severity and CFTR mediated residual chloride secretion.
    Species studied:
    Human
    Abstract:
    F508del-CFTR, the most frequent disease-causing mutation among Caucasian cystic fibrosis (CF) patients, has been characterised as a mutant defective in protein folding, processing and trafficking. We have investigated the two neighbouring cytokeratin genes KRT8 and KRT18 in a candidate gene approach to ask whether variants in KRT8 and/or KRT18 modify the impaired ion conductance known as the CF basic defect, and whether they are associated with correct trafficking of mutant CFTR and disease severity of CF.
  • Target disease:
    Cystic fibrosis (DOID_1485)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered severity 
    Evidence:
    From review article 
    Effect:
    Disease severity
    Alias in reference:
    KRT8:rs2035875
    Reference:
    PMID25053892
    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.