Polimorfismo Pro72Arg del gen TP53 se asocia a enfermedad coronaria en individuos chilenos / TP53 codon 72 polymorphism is associated with coronary artery disease in Chilean subjects

Introducción: Diferentes genes han sido implicados en la etiología de la enfermedad arterial coronaria, entre ellos, el gen TP53. Recientemente, el polimorfismo en el codon 72 (Pro72Arg, rs1042522) del gen TP53 fue señalado como factor de riesgo para enfermedad arterial coronaria. Sin embargo, otros autores no han confirmado esta observación. Así, en el presente estudio investigamos la posible asociación entre esta variante genética y la presencia de enfermedad arterial coronaria en individuos chilenos. Métodos: Se analizaron 209 pacientes, no relacionados, con diagnóstico de enfermedad arterial coronaria confirmada por angiografía (estenosis > 70 por ciento), 33 - 74 años y 216 individuos controles (30-68 años). Las concentraciones séricas de glucosa, acido úrico, triglicéridos, colesterol total y colesterol HDL fueron determinados por métodos enzimático-colorimétricos. El polimorfismo Pro72Arg del gen TP53 fue identificado mediante la técnica de reacción en cadena de polimerasa seguida de restricción enzimática (PCR-RFLP). Resultados: La distribución de genotipos para la mutación Pro72Arg del gen TP53 en pacientes y controles fue significativamente diferente (P=0.003). Adicionalmente, la frecuencia relativa de alelos fue tambiéndiferente (P=0.003). La OR para enfermedad coronaria relacionada al alelo 72Arg fue 2.0 (I.C.95 por ciento=1.33-2.90), confirmando la presencia de asociación. Por otro lado, no encontramos asociación entre los factores de riesgo tradicionales para enfermedad coronaria y los diferentes genotipos del polimorfismo Pro72Arg. Conclusión: Nuestro estudio muestra una interesante asociación entre enfermedad coronaria y el polimorfismo Pro72Arg del gen TP53 en individuos chilenos, sugiriendo que esta mutación podría ser útil como marcador genético de esta patología. Sin embargo, esta observación necesita ser reconfirmada con un estudio poblacional.

Different genes have been implicated in the aetiology of coronary artery disease, among these, the TP53 gene. Recently, the codon 72 polymorphism (Pro72Arg, rs1042522) of TP53 gene was indicated as a risk factor for coronary artery disease (CAD). However, other authors do not confirm this observation. Thus, in the present study we investigated the possible association between this genetic variant and the presence of CAD in Chilean subjects. Methods: 209 unrelated patients with diagnosis of CAD confirmed by angiography (33-74 years old) and 216 healthy controls (30 - 68 years old) were included in this study. The Pro72Arg polymorphism of the TP53 gene was evaluated by PCR-RFLP. Results: The genotype distribution for Pro72Arg variant of TP53 gene in CAD patients (PP: 6.2 percent, PR: 29.2 percent, RR: 64.6 percent) and controls (PP: 8.3 percent, PR: 43.5 percent, RR: 48.1 percent) was significantly different (P=0.003). Similarly, the allelicfrequency was also different (P = 0.003). The OR for CAD related to 72Arg allele was 2.0 (95 percent C.I. = 1.33 -2.90). Conclusion: These findings suggest that the Pro72Arg polymorphism of the TP53 gene is associated with CAD in study Chilean individuals.

Estrogen production by bovine binucleate and mononucleate trophoblastic cells in vitro.

The bovine placenta has long been known as a source of steroid hormones. We performed three experiments to compare production of estrogens by bovine mononucleate and binucleate trophoblastic cells and examined effects of cortisol, progesterone, pregnenolone, testosterone, and androstenedione. In the first experiment, binucleate trophoblastic cells were purified by unit gravity sedimentation from six enzymatically dispersed placentas between 150 and 180 days of gestation. Cells (8 x 10(5)/ml) were incubated first at 37 degrees C for 6 h with Medium 199 alone (M199/6h) or with 10(-7) M cortisol (cortisol/6h). Medium then was replaced with 10(-7) M progesterone, 10(-7) M pregnenolone, 10(-7) M testosterone, or M199, and a second incubation was conducted for 4 h. Estradiol production did not differ between cells incubated for the first 6 h in M199 vs. cortisol and was not affected by progesterone or pregnenolone. Testosterone increased (p < 0.05) estradiol production. Estrone production did not differ between cells incubated for the first 6 h in M199 vs. cortisol; estrone production was not affected by either progesterone, pregnenolone, or testosterone. Mononucleate as well as binucleate cells were purified from placentas between 165 and 180 days of gestation and used in two other experiments. In the first of these, enriched populations of binucleate and mononucleate cells were incubated first for 6 h with Medium 199 (M199) or 10(-7) M cortisol. Medium then was replaced with 10(-7) M testosterone, 10(-7) M androstenedione, or M199 and incubation continued for 4 h.(ABSTRACT TRUNCATED AT 250 WORDS)