RESUMO
The miRNA processing genes play essential roles in the biosynthesis of mammalian miRNAs, and their genetic variants are involved in the development of various cancers. Our study aimed to determine the potential association between miRNA processing gene polymorphisms and cervical precancerous lesions. Five single nucleotide polymorphisms (SNPs), including Ran-GTP (RAN) rs14035, exportin-5 (XPO5) rs11077, DICER1 rs3742330, DICER1 rs13078, and TARBP2 rs784567, were genotyped in a case-control study to estimate risk factors of cervical precancerous lesions. The gene-environment interactions and haplotype association were estimated. We identified a 27% decreased risk of cervical precancerous lesions for individuals with minor G allele in DICER1 rs3742330 (odds ratio (OR) = 0.73, 95% confidence interval (95% CI) = 0.58-0.92, P = 0.009). The AG and AG/GG genotypes in DICER1 rs3742330 were also found to decrease the risk of cervical precancerous lesions (AG compared with AA: OR = 0.51, 95% CI = 0.35-0.73, P <0.001; AG/GG compared with AA: OR = 0.54, 95% CI = 0.39-0.77, P = 0.001). The GT haplotype in DICER1 had a risk effect on cervical precancerous lesions compared with the AT haplotype (OR = 1.36, 95% CI = 1.08-1.73, P = 0.010). A two-factor (DICER1 rs3742330 and human papillomavirus (HPV) infection) and two three-factor (model 1: rs3742330, passive smoking, and HPV infection; model 2: rs3742330, abortion history, and HPV infection) interaction models for cervical precancerous lesions were identified. In conclusion, the genetic variants in the miRNA processing genes and interactions with certain environmental factors might contribute to the risk of cervical precancerous lesions in southern Chinese women.
Assuntos
RNA Helicases DEAD-box/genética , Predisposição Genética para Doença , Infecções por Papillomavirus/genética , Ribonuclease III/genética , Neoplasias do Colo do Útero/genética , Adulto , China , Feminino , Estudos de Associação Genética , Genótipo , Haplótipos/genética , Humanos , Carioferinas/genética , MicroRNAs/genética , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , Polimorfismo de Nucleotídeo Único/genética , Lesões Pré-Cancerosas , Gravidez , Proteínas de Ligação a RNA/genética , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/patologia , Proteína ran de Ligação ao GTP/genéticaRESUMO
BACKGROUND: Glaucoma is considered as a neurodegenerative disorder in which the optic nerve damage leads to irreversible blindness. Many scientific findings indicate miRNA implication in the neurodegeneration process. In this study, we aimed to evaluate the polymorphic variants of miRNA processing genes, RAN (rs14035) and GEMIN3 (rs197388), and their association with a risk of primary open-angle glaucoma (POAG) in relation to selected clinical parameters. MATERIALS AND METHODS: The study included 246 POAG patients and 188 controls. The selected gene polymorphisms were analyzed by TaqMan SNP Genotyping Assay using DNA extracted from blood samples. RESULTS: The obtained results indicated that the AA genotype of rs197388 as well as the A allele in the same gene may be associated with an elevated risk of POAG development (P = 0.021, P = 0.017 respectively). The correlation between the data and clinical parameters has shown that the A allele of rs197388 in relation to retinal nerve fiber layer(RNFL) could be responsible for an increased risk of glaucoma occurrence (P = 0.028), while the AT genotype could be associated with a decreased risk of POAG according to the mean deviation parameter (P = 0.023). CONCLUSION: Our data has shown that GEMIN3 gene (rs197388) polymorphisms might be associated with a risk of POAG development in the Polish population. This is the first report evaluating the polymorphic variants of miRNA processing genes, RAN and GEMIN3, with a changed risk of glaucoma.