MicroRNA binding mediated Functional sequence variant in 3\u2032-UTR of DNA repair Gene XPC in Age-related Cataract

Abstract

DNA oxidative damage repair is strongly involved in the pathogenesis of age-related cataract (ARC). The sequence variants of in coding region of DNA repair genes have been shown to be associated with ARC. It is known that single nucleotide polymorphisms (SNPs) in the 3′-terminal untranslated region (3′-UTR) can alter the gene expression by binding with microRNAs (miRNAs). We hypothesize that SNP(s) in miRNA binding site of certain DNA oxidative damage repair genes might associate with ARC risk. We examined 10 miRNA binding SNPs in 3′-UTR of 7 oxidative damage genes and revealed the XPC- rs2229090 C allele was associated with nuclear type of ARC (ARNC) risk in Chinese population. The individuals with the variant G allele (CG and GG) of XPC- rs2229090 had higher XPC mRNA expression compared to individuals carrying CC genotype. The in vitro assay showed that luciferase reporter gene expression can be down regulated by hsa-miR-589-5p in cells transfected with rs2229090 C allele compared to G allele. These results suggested that the C allele of XPC-2229090 increase the risk with ARNC. The mechanism underlying might be due to the stronger interation of the C allele with hsa-miR-589-5p, resulting in lower XPC expression and DNA repair capability than the individuals carring G allele in lens.