Variant "AGER:c.-429T>C"
Search results: 5 records
Variant information
Gene:
AGER 
Variant:
AGER:c.-429T>C 
Genomic location:
chr6:32152442(hg19) 
HGVS:
SO Term RefSeq
protein_coding NM_001206929.1.3:c.-443T>C
protein_coding NM_001136.4.3:c.-443T>C
protein_coding NM_001206932.1.6:c.-443T>C
protein_coding NM_001206934.1.5:c.-443T>C
protein_coding NM_001206936.1:c.-443T>C
protein_coding NM_001206940.1:c.-443T>C
protein_coding NM_001206954.1.2:c.-443T>C
protein_coding NM_001206966.1.3:c.-443T>C
protein_coding NM_172197.2.3:c.-443T>C
pseudogene NR_038190.1.2:n.-343T>C
protein_coding NM_006913.3:c.*4339A>G
pseudogene NR_003129.1:n.*3875A>G
pseudogene NR_106891.1:n.*4789A>G
protein_coding NM_002586.4:c.*1717T>C
AGER.5-PBX2:n.32152442A>G
show all
Alias:
AGER:rs1800625 
dbSNP ID:
rs1800625  
GWAS trait:
drug-induced agranulocytosis,treatment refractory schizophrenia,response to clozapine,cancer,response to pazopanib,serum alanine aminotransferase measurement 
Modifier statisitcs
Record:
5 
Disorder:
3 
Reference:
3 
Effect type:
Expressivity(4) ,Pleiotropy(1)  
Modifier effect:
Altered gene activity and Altered severity(3) ,Altered FEV(1)(1) ,Altered phenotype(1)  
Details：
  • Target disease:
    Abnormal Lung Morphology (HP:0002088)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered gene activity and Altered severity 
    Evidence:
    P=0.03 
    Effect:
    The functional promoter AGER -429C variant is associated with an increased RAGE expression that can lead to an increased lung inflammation and a more severe lung disease.
    Alias in reference:
    AGER:c.-429T>C
    Reference:
    PMID22860029
    Title:
    AGER -429T/C is associated with an increased lung disease severity in cystic fibrosis.
    Species studied:
    Human
    Abstract:
    The clinical course of cystic fibrosis (CF) varies between patients bearing identical CFTR mutations, suggesting the involvement of modifier genes. We assessed the association of lung disease severity with the variant AGER -429 T/C, coding for RAGE, a pro-inflammatory protein, in CF patients from the French CF Gene Modifier Study. We analyzed the lung function of 967 CF patients p.Phe508del homozygous. FEV(1) was analyzed as CF-specific percentile adjusted on age, height and mortality. AGER -429T/C polymorphism was genotyped and its function was evaluated in vitro by measurement of the luciferase activity. AGER -429 minor allele (C) was associated with poorer lung function (p = 0.03). In vitro, the promoter activity was higher in cells transfected with AGER -429C compared to cells transfected with the AGER -429T allele (p = 0.016 in BEAS-2B cells). AGER seems to be a modifier gene of lung disease severity in CF, and could be an interesting biomarker of CF airway inflammation. The functional promoter AGER -429C variant is associated with an increased RAGE expression that can lead to an increased lung inflammation and a more severe lung disease.
  • Target disease:
    Cystic fibrosis (DOID_1485)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered FEV(1) 
    Evidence:
    8.1ah comprises linked polymorphisms of major pro-inflammatory cytokines including lta, tnf, hsp and rage. On average, fev1 was significantly lower in 8.1 ah carriers (P<0.04). 
    Effect:
    These findings support the concept that 8.1AH is an important genetic modifier of lung disease in CF.
    Alias in reference:
    AGER:c.-429T>C
    Reference:
    PMID21993476
    Title:
    Ancestral haplotype 8.1 and lung disease severity in European cystic fibrosis patients.
    Species studied:
    Human
    Abstract:
    The clinical course of cystic fibrosis (CF) lung disease varies between patients bearing identical CFTR mutations. This suggests that additional genetic modifiers may contribute to the pulmonary phenotype. The highly conserved ancestral haplotype 8.1 (8.1AH), carried by up to one quarter of Caucasians, comprises linked gene polymorphisms on chromosome 6 that play a key role in the inflammatory response: LTA +252A/G; TNF -308G/A, HSP70-2 +1267A/G and RAGE -429T/C. As inflammation is a key component inducing CF lung damage, we investigated whether the 8.1AH represents a lung function modifier in CF.
  • Target disease:
    Cystic fibrosis (DOID_1485)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered gene activity and Altered severity 
    Evidence:
    P=0.016 
    Effect:
    The functional promoter AGER -429C variant is associated with an increased RAGE expression that can lead to an increased lung inflammation and a more severe lung disease.
    Alias in reference:
    AGER:c.-429T>C
    Reference:
    PMID22860029
    Title:
    AGER -429T/C is associated with an increased lung disease severity in cystic fibrosis.
    Species studied:
    Human
    Abstract:
    The clinical course of cystic fibrosis (CF) varies between patients bearing identical CFTR mutations, suggesting the involvement of modifier genes. We assessed the association of lung disease severity with the variant AGER -429 T/C, coding for RAGE, a pro-inflammatory protein, in CF patients from the French CF Gene Modifier Study. We analyzed the lung function of 967 CF patients p.Phe508del homozygous. FEV(1) was analyzed as CF-specific percentile adjusted on age, height and mortality. AGER -429T/C polymorphism was genotyped and its function was evaluated in vitro by measurement of the luciferase activity. AGER -429 minor allele (C) was associated with poorer lung function (p = 0.03). In vitro, the promoter activity was higher in cells transfected with AGER -429C compared to cells transfected with the AGER -429T allele (p = 0.016 in BEAS-2B cells). AGER seems to be a modifier gene of lung disease severity in CF, and could be an interesting biomarker of CF airway inflammation. The functional promoter AGER -429C variant is associated with an increased RAGE expression that can lead to an increased lung inflammation and a more severe lung disease.
  • Target disease:
    Cystic fibrosis (DOID_1485)
    Effect type:
    Pleiotropy 
    Modifier effect:
    Altered phenotype 
    Evidence:
    From review article 
    Effect:
    Lung disease
    Alias in reference:
    AGER:rs1800625
    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.
  • Target disease:
    Pleuritis (HP:0002102)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered gene activity and Altered severity 
    Evidence:
    P=0.016 
    Effect:
    The functional promoter AGER -429C variant is associated with an increased RAGE expression that can lead to an increased lung inflammation and a more severe lung disease.
    Alias in reference:
    AGER:c.-429T>C
    Reference:
    PMID22860029
    Title:
    AGER -429T/C is associated with an increased lung disease severity in cystic fibrosis.
    Species studied:
    Human
    Abstract:
    The clinical course of cystic fibrosis (CF) varies between patients bearing identical CFTR mutations, suggesting the involvement of modifier genes. We assessed the association of lung disease severity with the variant AGER -429 T/C, coding for RAGE, a pro-inflammatory protein, in CF patients from the French CF Gene Modifier Study. We analyzed the lung function of 967 CF patients p.Phe508del homozygous. FEV(1) was analyzed as CF-specific percentile adjusted on age, height and mortality. AGER -429T/C polymorphism was genotyped and its function was evaluated in vitro by measurement of the luciferase activity. AGER -429 minor allele (C) was associated with poorer lung function (p = 0.03). In vitro, the promoter activity was higher in cells transfected with AGER -429C compared to cells transfected with the AGER -429T allele (p = 0.016 in BEAS-2B cells). AGER seems to be a modifier gene of lung disease severity in CF, and could be an interesting biomarker of CF airway inflammation. The functional promoter AGER -429C variant is associated with an increased RAGE expression that can lead to an increased lung inflammation and a more severe lung disease.