RGD Reference Report - Thioredoxin reductase 1 haplotypes modify familial amyotrophic lateral sclerosis onset. - Rat Genome Database

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Thioredoxin reductase 1 haplotypes modify familial amyotrophic lateral sclerosis onset.

Authors: Mitchell, J  Morris, A  De Belleroche, J 
Citation: Mitchell J, etal., Free Radic Biol Med. 2009 Jan 15;46(2):202-11. Epub 2008 Oct 22.
RGD ID: 5685032
Pubmed: PMID:18996185   (View Abstract at PubMed)
DOI: DOI:10.1016/j.freeradbiomed.2008.09.041   (Journal Full-text)

Thioredoxin reductase 1 is a key enzyme in cellular redox processes, which are known to play a role in the pathogenesis of familial amyotrophic lateral sclerosis (FALS). The gene TXNRD1 was therefore screened for association with FALS. Resequencing of the exons and flanking regions identified 19 single-nucleotide polymorphisms (SNPs) of which 2, the intronic SNPs rs6539137 and rs4630362, were significantly associated with FALS. However, no association of rs6539137 with sporadic ALS was detected. The TXNRD1 haplotypes were reconstructed using the EH and PHASE 2.1 programs and also showed an association with FALS. Bayesian analysis of these SNP combinations, carried out using the BIMBAM program, indicated that rs10861192 strongly augmented this association. Indeed the haplotypes with minor alleles at both rs10861192 and rs6539137, although present in FALS, were totally absent from controls. Patients with the minor allele of rs6539137 were also associated with an early age at onset, which was decreased by 8 years. Furthermore the shift of onset was more pronounced in males and not significant in females. These results show that TXNRD1 may act as an important modifier gene of FALS and indicate that the additional thiol-redox system genes, thioredoxin and the peroxiredoxins, should also be investigated in FALS and other neurological disorders.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TXNRD1Humanamyotrophic lateral sclerosis susceptibilityIAGP DNA:SNPs:intron:rs6539137 and rs4630362 (human)RGD 
Txnrd1Ratamyotrophic lateral sclerosis susceptibilityISOTXNRD1 (Homo sapiens)DNA:SNPs:intron:rs6539137 and rs4630362 (human)RGD 
Txnrd1Mouseamyotrophic lateral sclerosis susceptibilityISOTXNRD1 (Homo sapiens)DNA:SNPs:intron:rs6539137 and rs4630362 (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Txnrd1  (thioredoxin reductase 1)

Genes (Mus musculus)
Txnrd1  (thioredoxin reductase 1)

Genes (Homo sapiens)
TXNRD1  (thioredoxin reductase 1)


Additional Information