Premium
A variant in 5‐UTR of ERCC6 protects against age‐related macular degeneration in European decent
Author(s) -
Tuo Jingsheng,
Cho Youngeun,
Chew Emily,
Chan ChiChao
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.926.10
Subject(s) - single nucleotide polymorphism , cockayne syndrome , biology , linkage disequilibrium , genetics , snp , nucleotide excision repair , macular degeneration , genotype , medicine , dna repair , ophthalmology , gene
Age‐related macular degeneration (AMD) is the leading cause of visual loss in aged people and has genetic components in its pathogenesis. ERCC6 functions in DNA repair and the disruption of ERCC6 is causal to Cockayne syndrome, a disorder featuring accelerated aging and progressive multi‐organ degeneration including retina. Previously we reported that a single nucleotide polymorphism (SNP) in ERCC6 regulatory region (rs3793784) was moderately associated with AMD. This study is to investigate the association of a set of SNPs in ERCC6 with AMD. We selected 12 common SNPs across ERCC6 and evaluated them in 162 advanced AMD cases and 189 controls. We identified that a C/A SNP in near 5′‐UTR of ERCC6 is highly associated with protection against AMD (odds ratio=0.33, p<0.01 after permutation correction). The SNP was close to the transcriptional starting site, suggesting a function of gene regulation. The SNP was in linkage disequilibrium with rs3793784 but has 2‐folds higher impact odds ratio. Interestingly, the control subjects with AA alleles (homozygous protective) had a higher average age than the controls with CC or CA. The genotypes were distributed evenly in dry and wet types of AMD. The SNP could result in the loss of Sp1 binding site and in the generation of a C/EBPalpha binding site. The underlying mechanism of this protective association may involve a SNP alteration of the regulatory function by an ERCC6 activator element.