Gene "PPARGC1A"
Found 5 records
Gene information
Gene symbol:
PPARGC1A
See related:
Ensembl: ENSG00000109819, Gene ID: 10891
Additive variants :
Undetected
Genetic interaction partners
No data
Modifier statisitcs
Record:
5 
Disorder:
2 
Vriant:
4 
Reference:
3 
Effect type:
Expressivity(5)  
Modifier effect:
Altered onset time(2) ,Altered severity(2) ,Risk factor(1)  
Details：
  • Variant 1:
    PPARGC1A:c.877+171A>C
    Gene:
    PPARGC1A
    Genomic location:
    chr4:23825732
    dbSNP ID:
    rs2290602
    Target disease:
    Nonalcoholic Fatty Liver Disease(DOID_0080208)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered severity 
    Evidence:
    P=<0.02 
    Effect:
    Associated with the development NAFLD or disease severity.
    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.
  • Variant 2:
    PPARGC1A:c.235-19637A>G
    Gene:
    PPARGC1A
    Genomic location:
    chr4:23853011
    dbSNP ID:
    rs7665116
    Alias:
    PPARGC1A:rs7665116
    Target disease:
    Huntington's Disease(DOID_12858)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    P=0.012 
    Effect:
    When combining these results with the previously described modifiers rs7665116 in PPARGC1A and C7028T in the cytochrome c oxidase subunit I (CO1, mt haplogroup H) in a multivariable model, a substantial proportion of the variation in AO can be explained by the joint effect of significant modifiers and their interactions,
    Reference:
    PMID21595933
    Title:
    PGC-1alpha downstream transcription factors NRF-1 and TFAM are genetic modifiers of Huntington disease.
    Species studied:
    Human
    Abstract:
    Huntington disease (HD) is an inherited neurodegenerative disease caused by an abnormal expansion of a CAG repeat in the huntingtin HTT (HD) gene. The primary genetic determinant of the age at onset (AO) is the length of the HTT CAG repeat; however, the remaining genetic contribution to the AO of HD has largely not been elucidated. Recent studies showed that impaired functioning of the peroxisome proliferator-activated receptor gamma coactivator 1a (PGC-1alpha) contributes to mitochondrial dysfunction and appears to play an important role in HD pathogenesis. Further genetic evidence for involvement of PGC-1alpha in HD pathogenesis was generated by the findings that sequence variations in the PPARGC1A gene encoding PGC-1alpha exert modifying effects on the AO in HD. In this study, we hypothesised that polymorphisms in PGC-1alpha downstream targets might also contribute to the variation in the AO.
  • Variant 3:
    PPARGC1A:c.235-19637A>G
    Gene:
    PPARGC1A
    Genomic location:
    chr4:23853011
    dbSNP ID:
    rs7665116
    Alias:
    PPARGC1A:rs7665116
    Target disease:
    Huntington's Disease(DOID_12858)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered onset time 
    Evidence:
    P<0.007 
    Effect:
    With the addition of each SNP-SNP interaction, along with each SNP's respective main effect, the variability in adjusted log motor AO increased
    Reference:
    PMID21595933
    Title:
    PGC-1alpha downstream transcription factors NRF-1 and TFAM are genetic modifiers of Huntington disease.
    Species studied:
    Human
    Abstract:
    Huntington disease (HD) is an inherited neurodegenerative disease caused by an abnormal expansion of a CAG repeat in the huntingtin HTT (HD) gene. The primary genetic determinant of the age at onset (AO) is the length of the HTT CAG repeat; however, the remaining genetic contribution to the AO of HD has largely not been elucidated. Recent studies showed that impaired functioning of the peroxisome proliferator-activated receptor gamma coactivator 1a (PGC-1alpha) contributes to mitochondrial dysfunction and appears to play an important role in HD pathogenesis. Further genetic evidence for involvement of PGC-1alpha in HD pathogenesis was generated by the findings that sequence variations in the PPARGC1A gene encoding PGC-1alpha exert modifying effects on the AO in HD. In this study, we hypothesised that polymorphisms in PGC-1alpha downstream targets might also contribute to the variation in the AO.
  • Variant 4:
    PPARGC1A:c.1835C>T(p.Thr612Met)
    Gene:
    PPARGC1A
    Genomic location:
    chr4:23814707
    dbSNP ID:
    rs3736265
    Target disease:
    Huntington's Disease(DOID_12858)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered onset time 
    Evidence:
    P=0.0164 
    Effect:
    A coding variant (rs3736265) in PPARGC1A is associated with an earlier motor AO in men but not women carrying the HD mutation.
    Reference:
    PMID24383721
    Title:
    A single nucleotide polymorphism in the coding region of PGC-1α is a male-specific modifier of Huntington disease age-at-onset in a large European cohort.
    Species studied:
    Human
    Abstract:
    Genetic modifiers are important clues for the identification of therapeutic targets in neurodegenerative diseases. Huntington disease (HD) is one of the most common autosomal dominant inherited neurodegenerative diseases. The clinical symptoms include motor abnormalities, cognitive decline and behavioral disturbances. Symptom onset is typically between 40 and 50 years of age, but can vary by several decades in extreme cases and this is in part determined by modifying genetic factors. The metabolic master regulator PGC-1α, coded by the PPARGC1A gene, coordinates cellular respiration and was shown to play a role in neurodegenerative diseases, including HD.
  • Variant 5:
    PPARGC1A:c.1444G>A(p.Gly482Ser)
    Gene:
    PPARGC1A
    Genomic location:
    chr4:23815662
    dbSNP ID:
    rs8192678
    Target disease:
    Nonalcoholic Fatty Liver Disease(DOID_0080208)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered severity 
    Evidence:
    P=0.008 
    Effect:
    Associated with the development NAFLD or disease severity.
    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.