RESUMO
BACKGROUND: Knowledge regarding genetic influences on eating behaviours is expanding; yet less is known regarding contributions of epigenetic variation to appetitive traits and body mass index (BMI) in children. OBJECTIVE: The purpose of this study was to explore relationships between methylation at differentially methylated regions (DMRs) of imprinted genes (insulin-like growth factor 2/H19 and Delta-like, Drosophila, homolog 1/maternally expressed gene 3) using DNA extracted from umbilical cord blood leucocytes, two genetically influenced appetitive traits (food responsiveness and satiety responsiveness) and BMI. METHODS: Data were obtained from participants (N = 317; mean age = 3.6 years; SD = 1.8 years) from the Newborn Epigenetic STudy. Conditional process models were implemented to investigate the associations between DMRs of imprinted genes and BMI, and test whether this association was mediated by appetitive traits and birthweight and moderated by sex. RESULTS: Appetitive traits and birthweight did not mediate the relationship between methylation at DMRs. Increased insulin-like growth factor 2 DMR methylation was associated with higher satiety responsiveness. Higher satiety responsiveness was associated with lower BMI. Associations between methylation at DMRs, appetitive traits and BMI differed by sex. CONCLUSIONS: This is one of the first studies to demonstrate associations between epigenetic variation established prior to birth with appetitive traits and BMI in children, providing support for the need to uncover genetic and epigenetic mechanisms for appetitive traits predisposing some individuals to obesity.
Assuntos
Apetite/genética , Índice de Massa Corporal , Metilação de DNA/genética , Comportamento Alimentar/fisiologia , Impressão Genômica/genética , Peso ao Nascer/genética , Proteínas de Ligação ao Cálcio , Criança , Pré-Escolar , Epigênese Genética/genética , Feminino , Sangue Fetal/metabolismo , Humanos , Lactente , Recém-Nascido , Fator de Crescimento Insulin-Like II/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Proteínas de Membrana/genética , Fenótipo , Gravidez , Fatores Sexuais , Inquéritos e QuestionáriosRESUMO
Screening for uterine cervical intraepithelial neoplasia (CIN) followed by aggressive treatment has reduced invasive cervical cancer (ICC) incidence and mortality. However, ICC cases and carcinoma in situ (CIS) continue to be diagnosed annually in the United States, with minorities bearing the brunt of this burden. Because ICC peak incidence and mortality are 10-15 years earlier than other solid cancers, the number of potential years of life lost to this cancer is substantial. Screening for early signs of CIN is still the mainstay of many cervical cancer control programs. However, the accuracy of existing screening tests remains suboptimal. Changes in epigenetic patterns that occur as a result of human papillomavirus infection contribute to CIN progression to cancer, and can be harnessed to improve existing screening tests. However, this requires a concerted effort to identify the epigenomic landscape that is reliably altered by HPV infection specific to ICC, distinct from transient changes.
Assuntos
Epigênese Genética/genética , Etnicidade/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/mortalidade , Feminino , Humanos , Incidência , Taxa de Sobrevida , Neoplasias do Colo do Útero/genéticaRESUMO
Binding of [3H]cocaine to membrane preparations from whole fetal rat brain was studied. High-affinity binding (10 nM cocaine) was detected as early as gestational day (GD) 15 and steadily increased across subsequent development. Saturation studies comparing [3H]cocaine binding at GD20 and adulthood yielded similar KD values, and LIGAND analyses favored a two-site model if an extended range of [3H]cocaine concentrations was used. Various monoamine uptake inhibitors displaced labeled cocaine with potencies consistent with the idea that [3H]cocaine labels the dopamine (DA), serotonin (5-HT), and possibly also the norepinephrine (NE) transporters in whole fetal brain preparations. Synaptosomal DA uptake was well developed by GD20, as was the potency of cocaine to inhibit such uptake. The results indicate that functional, monoamine transporter related cocaine binding sites are present in the fetal rat brain. Such sites are likely to play an important role in mediating the direct interactions of prenatally-administered cocaine with developing monoaminergic systems in both animals and humans.