RESUMEN
INTRODUCTION: Oxidative stress is a key factor in the pathogenesis of intra-uterine growth restriction in singleton. However, its role in selective intra-uterine growth restriction (sIUGR) in monochorionic twins (MCT) is still unknown. This study explored the characteristics of oxidative stresses in the placenta shares of MCT and analyzed their possible connections with sIUGR. METHODS: The placental levels of hypoxia inducible factor-1α gene (HIF1A)mRNA, malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG) were evaluated in normal MCT (Group A) and sIUGR MCT (Group B). The results were compared between the placental shares of the larger twins (A1/B1) and smaller twins (A2/B2). RESULTS: Placental HIF1A mRNA level significantly increased in Group B. Particularly, HIF1A mRNA level was elevated in the placenta share of the growth-restricted fetus (B2) than the co-twin (B1) (P = 0.036). More discordant HIF1A mRNA level was detected in Group B than Group A with larger inter-twin difference (P = 0.021). The levels of MDA and 8-OHdG were significantly higher in B2 than B1 in sIUGR MCT (P < 0.05). Both the inter-twin differences of MDA and 8-OHdG were also significantly larger in Group B (P < 0.05), indicating that discordant oxidative stress existed in the placental shares of sIUGR pregnancies. Finally, MDA concentration was found inversely correlated with neonatal birth weight, in both sIUGR (r = -0.650, P = 0.022) and normal MCT (r = -0.632, P = 0.027) pregnancies. DISCUSSION: The elevation of HIF1A mRNA, and MDA/8-OHdG levels in placenta shares of sIUGR MCT suggests that oxidative stress may be involved in the pathogenesis of sIUGR.
Asunto(s)
Enfermedades en Gemelos/metabolismo , Retardo del Crecimiento Fetal/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Estrés Oxidativo , Placenta/metabolismo , Embarazo Gemelar/metabolismo , ARN Mensajero/metabolismo , Regulación hacia Arriba , 8-Hidroxi-2'-Desoxicoguanosina , Adulto , Biomarcadores/metabolismo , Peso al Nacer , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Enfermedades en Gemelos/patología , Femenino , Retardo del Crecimiento Fetal/patología , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Peroxidación de Lípido , Masculino , Malondialdehído/metabolismo , Placenta/patología , EmbarazoRESUMEN
Host genetic factors and environment factors including hepatitis B virus (HBV) genotypes are widely studied for the different outcomes of HBV infection. Recent studies suggest that tumour necrosis factor-alpha (TNF-alpha) plays a pivotal role in the viral clearance and host immune response to HBV, and the capacity for TNF-alpha production in individuals is influenced by a major genetic component. In this study, we aimed to explore whether the single-nucleotide polymorphisms (SNPs) of TNF-alpha promoter are associated with the outcomes of HBV infection in the Chinese Han population. One hundred and forty-three spontaneously recovered HBV subjects and 196 chronic hepatitis B patients were recruited in this case-control study in the Beijing area of China. Polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) and sequence-specific primer-PCR (SSP-PCR) were used to detect the SNPs of five sites in the TNF-alpha promoter (-238G/A, -308G/A, -857C/T, -863C/A, -1031T/C). The frequency distributions of genotypes and haplotypes in two groups were analysed by EPI and EH programs. The presence of the -238GG genotype was significantly correlated with persistence of HBV infection (OR = 4.08, P = 0.02), and -857TT genotype appeared in relation to the spontaneous clearance of HBV (OR = 0.47, P = 0.03). Frequency of haplotype GGCCT (-238/-308/-857/-863/-1031) in the chronic HB group was significantly lower than that in spontaneously recovered group (P = 0.03), and frequencies of haplotypes GGCAT and GGTAT in the chronic HB group were significantly higher than those in the spontaneously recovered group (P = 0.0001, P = 0.0004). In conclusion, TNF-alpha promoter polymorphisms are independently associated with different outcomes of HBV infection.