ABSTRACT
OBJECTIVE: The apoptotic genes Bax and Bcl-2 are both involved in the pathogenesis of preterm delivery in conjunction with additional factors. We characterized gene expression patterns of these apoptotic regulatory genes as well as relevant environmental factors. DESIGN: A gene expression study with evaluation of clinical data. SETTING: Semmelweis University, Budapest, Hungary. SAMPLE: Human placental samples from 104 preterm and 140 full-term pregnancies. METHODS: Gene tests were performed using real-time PCR to assess gene expression patterns of Bax and Bcl-2 in human placental samples. Clinical data were collected from our computerized database. MAIN OUTCOME MEASURES: Apoptotic gene expression pattern and clinical information against the background of preterm delivery. RESULTS: In placental samples from preterm delivery pregnancies, expression of the Bcl-2 gene was unchanged, whereas the Bax gene was overexpressed. Placental gene expression of Bax in preterm delivery was dependent on gestational age with gestational weeks 28-32 and 32-36 associated with overexpression, and no overexpression in gestational weeks 24-28. Preterm delivery began with premature rupture of membranes in 70.2% and spontaneous uterine activity in 29.8%. CONCLUSIONS: The Bax gene was overexpressed in preterm delivery, whereas expression of the Bcl-2 gene remained unchanged. After the 28(th) gestational week, apoptosis appears to be a key factor in the pathogenesis of preterm delivery.
Subject(s)
Gene Expression , Genes, bcl-2 , Placenta/metabolism , Premature Birth/genetics , Proto-Oncogene Proteins c-bcl-2/genetics , bcl-2-Associated X Protein/genetics , Adult , Case-Control Studies , Female , Gene Expression Profiling , Genetic Markers , Humans , Infant, Newborn , Male , Pregnancy , Premature Birth/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Real-Time Polymerase Chain Reaction , Up-Regulation , bcl-2-Associated X Protein/metabolismABSTRACT
Cardiovascular diseases (CVDs) are the leading causes of death in the developed countries. Elevated homocysteine level is as an independent risk factor of CVDs. The C677T and A1298C variants of methylenetetrahydrofolate reductase gene (MTHFR) have been shown to influence folate and homocysteine metabolisms. However, the relationship between MTHFR polymorphisms and hyperhomocysteinemia has not been well established yet. The gene variants were also reported to be associated with CVDs. In addition, the C677T polymorphisms may play a role in the development of hypertension. Recent research evidence has suggested that MTHFR variants might be independently linked to CVDs and hypertension, because of the involvement of the MTHFR enzyme product (5-methyl-tetrahydrofolate /5-MTHF) in the regulation of endothelial functions. Further research is required to investigate the association between gene polymorphisms of folate-metabolizing enzymes and CVDs, and to identify the possible role of the relevant gene variants in the molecular pathogenesis of hyperhomocysteinemia.
