Variant "P4HB:c.*600G>T"
Search result: 1 record
Variant information
Gene:
P4HB 
Variant:
P4HB:c.*600G>T 
Genomic location:
chr17:79801288(hg19) 
HGVS:
SO Term RefSeq
protein_coding NM_000918.3:c.*600G>T
dbSNP ID:
rs8324  
GWAS trait:
no data 
Modifier statisitcs
Record:
1 
Disorder:
1 
Reference:
1 
Effect type:
Expressivity(1)  
Modifier effect:
Risk factor(1)  
Detail：
  • Target disease:
    Amyotrophic Lateral Sclerosis (DOID_332)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    P=0.0148 
    Effect:
    P4HB is a modifier gene in ALS susceptibility and may represent a potential therapeutic target for ALS.
    Reference:
    PMID23337974
    Title:
    Association studies indicate that protein disulfide isomerase is a risk factor in amyotrophic lateral sclerosis.
    Species studied:
    Human
    Abstract:
    Protein disulfide isomerase (PDI) plays an important role in the endoplasmic reticulum (ER) by facilitating the exchange of disulfide bonds and, together with other ER stress proteins, is induced in amyotrophic lateral sclerosis (ALS). However, genetic polymorphisms in the P4HB gene, which encodes PDI, have not been thoroughly investigated in ALS cases. In this study, we determined whether single-nucleotide polymorphisms (SNPs) in the P4HB gene were associated with familial ALS (FALS) and sporadic ALS (SALS). We report significant genotypic associations for two SNPs in P4HB with FALS, rs876016 (P=0.0198) and rs2070872 (P=0.0046), all values being FDR corrected. Significant allelic associations were also obtained for rs876016 with FALS (P=0.0155) and ALS (FALS and SALS) (P=0.0148). Four SNP haplotypes, which included two additional flanking SNPs, rs876017 and rs8324, were examined and rare haplotypes were found to be more common in ALS cases compared to controls. Seven haplotypes were significantly associated with FALS and one haplotype was significantly associated with SALS. One rare haplotype, which was present in controls, was overrepresented in a group of SOD1-positive FALS cases. Reduced survival was observed in FALS cases possessing at least one copy of the minor allele of rs2070872 (P=0.0059) and rs8324 (P=0.0167) and in individuals lacking the homozygous AAAC/AAAC diplotype (P=0.011). The results suggest that P4HB is a modifier gene in ALS susceptibility and may represent a potential therapeutic target for ALS.