Variant "GCLC:c.-594C>T"
Search results: 4 records
Variant information
Gene:
GCLC 
Variant:
GCLC:c.-594C>T 
Genomic location:
chr6:53410037(hg19) 
HGVS:
SO Term RefSeq
protein_coding NM_001498.3:c.-594C>T
protein_coding NM_001197115.1:c.-594C>T
GCLC-LOC101927136:n.53410037G>A
Alias:
GCLC:-129C>T, GCLC:c.-129T/C 
dbSNP ID:
rs17883901  
GWAS trait:
no data 
Modifier statisitcs
Record:
4 
Disorder:
3 
Reference:
4 
Effect type:
Expressivity(4)  
Modifier effect:
Altered severity(3) ,Risk factor(1)  
Details：
  • Target disease:
    Coronary Artery Disease (DOID_3393)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    OR=3.22, P=0.03 
    Effect:
    The two promoter polymorphisms of GCLM (-588C/T) and GCLC (-128T/C) are associated with an increased risk of IHD in Kazakhstan population.
    Alias in reference:
    GCLC:c.-129T/C
    Reference:
    PMID28757675
    Title:
    Association of GCLM -588C/T and GCLC -129T/C Promoter Polymorphisms of Genes Coding the Subunits of Glutamate Cysteine Ligase with Ischemic Heart Disease Development in Kazakhstan Population.
    Species studied:
    Human
    Abstract:
    Glutamate cysteine ligase (GCL) is a rate-limiting enzyme in synthesis of glutathione. Evidence suggests that genetic variations in the promoter region of genes coding a catalytic subunit (GCLC -129T/C) and a modifier subunit (GCLM -588C/T) of GCL have a functional impact on their transcriptional activity and were associated with various disorders. Hence, we hypothesize whether these two polymorphic variants of GCLM and GCLC genes are associated with the risk of ischemic heart disease (IHD) development in the population of Kazakhstan.
  • Target disease:
    Cystic fibrosis (DOID_1485)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered severity 
    Evidence:
    Balance testing accuracy=0.6824, P=0.008 
    Effect:
    Polymorphisms in genes associated with metabolism of GSH act on the CF's severity.
    Alias in reference:
    GCLC:-129C>T
    Reference:
    PMID23758905
    Title:
    Genetic interaction of GSH metabolic pathway genes in cystic fibrosis.
    Species studied:
    Human
    Abstract:
    Cystic fibrosis (CF) is a monogenic disease caused by CFTR gene mutations, with clinical expression similar to complex disease, influenced by genetic and environmental factors. Among the possible modifier genes, those associated to metabolic pathways of glutathione (GSH) have been considered as potential modulators of CF clinical severity. In this way it is of pivotal importance investigate gene polymorphisms at Glutamate-Cysteine Ligase, Catalytic Subunit (GCLC), Glutathione S-transferase Mu 1 (GSTM1), Glutathione S-transferase Theta 1 (GSTT1), and Glutathione S-transferase P1 (GSTP1), which have been associated to the GSH metabolic pathway and CF clinical severity.
  • Target disease:
    Cystic fibrosis (DOID_1485)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered severity 
    Evidence:
    P=0.044 
    Effect:
    CF severity is associated with polymorphisms in GSH pathways and CFTR mutations
    Alias in reference:
    GCLC:-129C>T
    Reference:
    PMID24593045
    Title:
    Polymorphisms in the glutathione pathway modulate cystic fibrosis severity: a cross-sectional study.
    Species studied:
    Human
    Abstract:
    Cystic fibrosis (CF) clinically manifests with various levels of severity, which are thought to be modulated by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR), modifier genes, and the environment. This study verified whether polymorphisms in modifier genes associated with glutathione (GSH) metabolism influence CF severity.
  • Target disease:
    Nonalcoholic Fatty Liver Disease (DOID_0080208)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered severity 
    Evidence:
    P=0.007 
    Effect:
    Associated with the development NAFLD or disease severity.
    Alias in reference:
    GCLC:c.-594C>T
    Reference:
    PMID26740948
    Title:
    Genetic analysis of nonalcoholic fatty liver disease within a Caribbean-Hispanic population.
    Species studied:
    Human
    Abstract:
    We explored potential genetic risk factors implicated in nonalcoholic fatty liver disease (NAFLD) within a Caribbean-Hispanic population in New York City. A total of 316 individuals including 40 subjects with biopsy-proven NAFLD, 24 ethnically matched non-NAFLD controls, and a 252 ethnically mixed random sampling of Bronx County, New York were analyzed. Genotype analysis was performed to determine allelic frequencies of 74 known single-nucleotide polymorphisms (SNPs) associated with NAFLD risk based on previous genome-wide association study (GWAS) and candidate gene studies. Additionally, the entire coding region of PNPLA3, a gene showing the strongest association to NAFLD was subjected to Sanger sequencing. Results suggest that both rare and common DNA variations in PNPLA3 and SAMM50 may be correlated with NAFLD in this small population study, while common DNA variations in CHUK and ERLIN1, may have a protective interaction. Common SNPs in ENPP1 and ABCC2 have suggestive association with fatty liver, but with less compelling significance. In conclusion, Hispanic patients of Caribbean ancestry may have different interactions with NAFLD genetic modifiers; therefore, further investigation with a larger sample size, into this Caribbean-Hispanic population is warranted.