Linking genotype to trophoblast phenotype in preeclampsia and HELLP syndrome associated with STOX1 genetic variants.

Preeclampsia is a major hypertensive pregnancy disorder with a 50% heritability. The first identified gene involved in the disease is STOX1, a transcription factor, whose variant Y153H predisposes to the disease. Two rare mutations were also identified in Colombian women affected by the hemolysis, elevated liver enzyme, low platelet syndrome, a complication of preeclampsia (T188N and R364X). Here, we explore the effects of these variants in trophoblast cell models (BeWo) where STOX1 was previously invalidated. We firstly showed that STOX1 knockout alters response to oxidative stress, cell proliferation, and fusion capacity. Then, we showed that mutant versions of STOX1 trigger alterations in gene profiles, growth, fusion, and oxidative stress management. The results also reveal alterations of the STOX interaction with DNA when the mutations affected the DNA-binding domain of STOX1 (Y153H and T188N). We also reveal here that a major contributor of these effects appears to be the E2F3 transcription factor.

Genómica funcional y medicina molecular del siglo XXI / Functional genomics and molecular medicine in the 21st century

Durante la última década del siglo pasado, en decenas de laboratorios de investigación científica, se desarrolló en una aparente calma la carrera que condujo al inicio de una nueva era de la investigación biomédica y de la medicina molecular. Lo cierto es que prestigiosos científicos, como James Watson, descubridor de la estructura del ADN y ganador del premio Nobel de Medicina en 1962, o Craig Venter, un excéntrico investigador disidente de la academia, protagonizaban una frenética competencia. Estos y otros genios-orates trabajaban por un mismo objetivo: la descripción del primer genoma humano (GH). Entre el 2000 y 2001, luego de años de trabajo y de un emocionante photofinish científico, finalmente se reportó la información correspondiente al patrimonio genético de la especie hu-mana. Diez años han transcurrido desde entonces y poco o nada se habla en los medios clínicos y académicos del país sobre el alcance de estas investigaciones y sobre la evolución de sus aplicaciones. ¿Qué representa para la comunidad médica y científica, para los pacientes y para la población sana la información contenida en el GH?

During the last decade of the last century, in dozens of scientific research laboratories, the race that led to the beginning of a new era of biomedical research and molecular medicine developed in apparent calm. The truth is that prestigious scientists, such as James Watson, discoverer of the structure of DNA and winner of the Nobel Prize for Medicine in 1962, or Craig Venter, an eccentric researcher who dissented from academia, were engaged in a frenetic competition. These and other genius-orates were working towards the same goal: the description of the first human genome (HG). Between 2000 and 2001, after years of work and an exciting scientific photofinish, the information corresponding to the genetic heritage of the human species was finally reported. Ten years have passed since then and little or nothing is said in the country's clinical and academic circles about the scope of this research and the evolution of its applications. What does the information contained in the GH represent for the medical and scientific community, for patients and for the healthy population?