PhenoModifier-Variant Detail

Variant "PPARGC1A:c.235-19637A>G"

Search results: 2 records

Variant information

Gene:

PPARGC1A

Variant:

PPARGC1A:c.235-19637A>G

Genomic location:

chr4:23853011(hg19)

HGVS:

SO Term	RefSeq
protein_coding	NM_013261.3:c.235-19637A>G

Alias:

PPARGC1A:rs7665116

dbSNP ID:

rs7665116

GWAS trait:

no data

Modifier statisitcs

Record:

2

Disorder:

1

Reference:

1

Effect type:

Expressivity(2)

Modifier effect:

Altered onset time(1) ,Risk factor(1)

Details：

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,

Alias in reference:

PPARGC1A:c.235-19637A>G

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.
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

Alias in reference:

PPARGC1A:rs7665116

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.