Receptor de estrógenos: variantes genéticas del ESR1 y parámetros bioquímicos de riesgo cardiovascular

El estudio de la asociacion entre marcadores geneticos y signos clinicos y/o bioquimicos de determinadas patologias, se ha propuesto para evaluar la posible utilidad clinica de emplear las determinaciones geneticas como predictores de riesgo. La enfermedad cardiovascular es una de las principales causas de muerte en mujeres posmenopausicas en el mundo occidental, hecho atribuido al descenso de los niveles de estrogenos circulantes. El objetivo de este trabajo fue investigar la existencia de asociaciones entre los polimorfismos del gen del receptor de estrogenos ESR1 (PvuII y XbaI) y los marcadores bioquimicos de riesgo cardiovascular en una poblacion local de mujeres sanas fertiles y posmenopausicas. Se clasifico a ambas poblaciones en subgrupos segun el marcador genetico 1(P/p), 2(p/p), 3(P/P), A(X/x), B(x/x), C(X/X), donde P/X indica ausencia de corte y p/x indica presencia de corte para PvuII y XbaI respectivamente. En una muestra de sangre periferica, se determinaron parametros bioquimicos de perfil lipidico, hemostasia e inflamacion y se compararon fertiles vs. posmenopausicas agrupadas segun el genotipo. Las mujeres posmenopausicas con genotipo A presentaron un aumento significativo en los niveles de colesterol total; C-LDL y trigliceridos respecto a las fertiles. En el subgrupo 1 se detectaron cambios solo en CT y C-LDL. En el haplotipo 1A de posmenopausicas solo se evidencio aumento en colesterol total. Los parametros de la hemostasia y de inflamacion no mostraron cambios significativos entre fertiles y posmenopausicas en funcion del marcador genetico presente. Los resultados sugieren que, el genotipo A identifica a la poblacion de mujeres posmenopausicas con un perfil lipidico mas desfavorable respecto a las fertiles del mismo subtipo. Los autores declaran no poseer conflictos de interes.(AU) In the last few years, the study of the association between genetic markers and clinical or biochemical signs of certain diseases, has been proposed to assess whether genetic determinations would be useful as risk predictors. Cardiovascular disease is a major cause of death in postmenopausal women in the Western world, fact attributed to the decline in circulating estrogen levels. The aim of the present study was to investigate the existence of associations between polymorphisms of the estrogen receptor ESR1 (PvuII and XbaI) and biochemical markers of cardiovascular risk, in a local population healthy childbearing potential and postme-nopausal women. Both populations were classified into subgroups according to the presence of specific genetic markers as follows: 1 (P / p), 2 (p / p), 3 (P / P), A (X / x), B (x / x), C (X / X), where P/ X = no cut site, and p / x = presence of cut site to restriction enzymes PvuII and XbaI respectively. In a peripheral blood sample biochemical markers of lipid profile, hemostasis and inflammation were determined, and comparisons were performed between fertile and postmenopausal women, grouped according to each genotype. Postmeno-pausal women with genotype A showed a significant increase in total cholesterol, LDL-C and triglycerides when compared women of childbearing potential with genotype A. In the subgroup 1, statistical changes in CT, C-LDL were detected. When haplotype analysis was performed, only one biochemical marker exhibited changes. In postmenopausal women positive to 1A haplotype, total cholesterol was slightly increased as compared to 1A haplotype women of childbearing potential. Hemostasis and inflammation markers did not show significant changes between women of childbearing potential and postmenopausal women grouped according to the polymorphism present. The results suggest that genotype A identifies the population of postmenopausal women population with a less favourable lipid profile compared to women of childbearing potential subtype. No financial conflicts of interest exist.(AU)