RGD Reference Report - The ERCC6 gene and age-related macular degeneration. - Rat Genome Database

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The ERCC6 gene and age-related macular degeneration.

Authors: Baas, DC  Despriet, DD  Gorgels, TG  Bergeron-Sawitzke, J  Uitterlinden, AG  Hofman, A  Van Duijn, CM  Merriam, JE  Smith, RT  Barile, GR  Ten Brink, JB  Vingerling, JR  Klaver, CC  Allikmets, R  Dean, M  Bergen, AA 
Citation: Baas DC, etal., PLoS One. 2010 Nov 1;5(11):e13786. doi: 10.1371/journal.pone.0013786.
RGD ID: 10401096
Pubmed: PMID:21072178   (View Abstract at PubMed)
PMCID: PMC2967476   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0013786   (Journal Full-text)

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the developed countries and is caused by both environmental and genetic factors. A recent study (Tuo et al., PNAS) reported an association between AMD and a single nucleotide polymorphism (SNP) (rs3793784) in the ERCC6 (NM_000124) gene. The risk allele also increased ERCC6 expression. ERCC6 is involved in DNA repair and mutations in ERCC6 cause Cockayne syndrome (CS). Amongst others, photosensitivity and pigmentary retinopathy are hallmarks of CS. METHODOLOGY/PRINCIPAL FINDINGS: Separate and combined data from three large AMD case-control studies and a prospective population-based study (The Rotterdam Study) were used to analyse the genetic association between ERCC6 and AMD (2682 AMD cases and 3152 controls). We also measured ERCC6 mRNA levels in retinal pigment epithelium (RPE) cells of healthy and early AMD affected human donor eyes. Rs3793784 conferred a small increase in risk for late AMD in the Dutch population (The Rotterdam and AMRO-NL study), but this was not replicated in two non-European studies (AREDS, Columbia University). In addition, the AMRO-NL study revealed no significant association for 9 other variants spanning ERCC6. Finally, we determined that ERCC6 expression in the human RPE did not depend on rs3793784 genotype, but, interestingly, on AMD status: Early AMD-affected donor eyes had a 50% lower ERCC6 expression than healthy donor eyes (P = 0.018). CONCLUSIONS/SIGNIFICANCE: Our meta-analysis of four Caucasian cohorts does not replicate the reported association between SNPs in ERCC6 and AMD. Nevertheless, our findings on ERCC6 expression in the RPE suggest that ERCC6 may be functionally involved in AMD. Combining our data with those of the literature, we hypothesize that the AMD-related reduced transcriptional activity of ERCC6 may be caused by diverse, small and heterogeneous genetic and/or environmental determinants.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ERCC6Humanmacular degeneration onsetIEP  RGD 
Ercc6Ratmacular degeneration onsetISOERCC6 (Homo sapiens) RGD 
Ercc6Mousemacular degeneration onsetISOERCC6 (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ercc6  (ERCC excision repair 6, chromatin remodeling factor)

Genes (Mus musculus)
Ercc6  (excision repair cross-complementing rodent repair deficiency, complementation group 6)

Genes (Homo sapiens)
ERCC6  (ERCC excision repair 6, chromatin remodeling factor)


Additional Information