RESUMEN
Aims: Paternal age is increasing in developed countries. Understanding of aging-related epigenetic changes in sperm is needed as well as factors that modify such changes. Materials & methods: Young pubertal and mature rats were exposed perinatally to vehicle or environmental xenobiotic 2,2',4,4'-tetrabromodiphenyl ether. Epididymal sperm was reduced representation bisulfite sequenced. Differentially methylated regions (DMRs) were identified via MethPipe. Results: In control animals, 5319 age-dependent DMRs were identified. Age-related DMRs were enriched for embryonic development. In exposed rats, DNA methylation was higher in young and lower in mature animals then in controls. Conclusions: Sperm methylome undergoes significant age-dependent changes, which may represent a causal link between paternal age and offspring phenotype. Environmental xenobiotics can interfere with the natural process of epigenetic aging.
Asunto(s)
Envejecimiento/fisiología , Metilación de ADN/efectos de los fármacos , Retardadores de Llama/efectos adversos , Espermatozoides/efectos de los fármacos , Animales , Desarrollo Embrionario/efectos de los fármacos , Epigénesis Genética/efectos de los fármacos , Epigenoma/efectos de los fármacos , Epigenómica/métodos , Femenino , Masculino , Parto/efectos de los fármacos , Edad Paterna , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Ratas , Ratas WistarRESUMEN
Aim: The purpose of our study was to analyze the predictive ability of the multiplicative model of genetic risk of nonlacunar ischemic stroke (IS) for independent samples from Russia. Patients & methods: A total of 181 patients and 360 healthy controls were included in this study. The discriminative accuracy of model was evaluated by the area under the receiver operating characteristic curve (AUC). Results: Classification model based on 15 single-nucleotide polymorphisms (SNPs), which are associated with a cardioembolic subtype of IS, had an AUC of 0.62 in patients with corresponding subtypes and an AUC of 0.58 for all patients. Conclusion: Risk calculation approach based on IS-associated SNPs had satisfactory performance in predicting the predisposition to the disease.