title: Functional SNP in 3'-UTR MicroRNA-Binding Site of ZNF350 Confers Risk for Age-Related Cataract.
abstract: Many studies have suggested that individual susceptibility to age-related cataract (ARC) may be associated with DNA sequence polymorphisms affecting gene regulation. As DNA repair is implicated in ARC pathogenesis and single-nucleotide polymorphisms (SNPs) in the 3'-terminal untranslated region (3'-UTR) targeted by microRNAs (miRNAs) can alter the gene function, we hypothesize that the miRNA-binding SNPs (miRSNPs) in DNA double-strand break repair (DSBR) and nucleotide excision repair (NER) pathways might associate with ARC risk. We genotyped nine miRSNPs of eight genes in DSBR and NER pathways in Chinese population and found that ZNF350- rs2278414:G>A was significantly associated with ARC risk. Even though the Comet assay of cellular DNA damage indicated that all the subtypes of ARC patients had more DNA breaks in peripheral lymphocytes than the controls independent of rs2278414 genotypes, individuals carrying the variant A allele (AA and AG) had lower ZNF350 mRNA levels compared with individuals with GG genotype. Moreover, the in vitro experiment indicated that miR-21-3p and miR-150-5p specifically downregulated luciferase reporter expression in the cell lines transfected with rs2278414 A allele compared with rs2278414 G. These results suggested that the association of SNP rs2278414 with ARC might involve an altered miRNA regulation of ZNF350.
authors: Eye Institute, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
authors: Shanshan
authors: S
authors: Gu
authors: Eye Institute, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
authors: Han
authors: H
authors: Rong
authors: Eye Institute, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
authors: Guowei
authors: G
authors: Zhang
authors: Eye Institute, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
authors: Lihua
authors: L
authors: Kang
authors: Eye Institute, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
authors: Mei
authors: M
authors: Yang
authors: Eye Institute, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China. guanhjeye@163.com.
authors: Huaijin
authors: H
authors: Guan
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D044466:Asian People / Q000235:genetics; D001665:Binding Sites; D002386:Cataract / Q000235:genetics*; D002681:China; D015536:Down-Regulation; D005260:Female; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D012097:Repressor Proteins; C533097:MIR150, human; C524940:MIRN21 microRNA, human; C422407:ZNF350 protein, human
keywords: 3′-UTR; MicroRNA; SNP; ZNF350; age-related cataract