RESUMEN
Transcriptional regulation of the cholesterol 7alpha-hydroxylase (CYP7AI) gene is of critical importance for bile acid and cholesterol metabolism. We evaluated the physiological significance of two common polymorphisms (-203C/A and -469T/C) in the promoter region of the CYP7AI gene. No evidence was found for physiological differences between either the -203C and -203A alleles or the -469T and -469C alleles in transient transfection studies using native 834bp promoter constructs. Moreover, no association was observed between the CYP7AI promoter polymorphisms and the hepatic cholesterol 7alpha-hydroxylase activity and parameters of bile acid synthesis rates, as analyzed in subjects with gallstone disease. In addition, no relationships were found between the promoter polymorphisms and plasma LDL cholesterol concentration in association studies conducted in three different groups of middle-aged Swedish men. Finally, near complete allelic association was found between the two promoter polymorphisms and the IVS6+363G/A polymorphism at the 3' end of the CYP7AI gene (|D'|=0.98), indicating strong linkage disequilibrium across the whole CYP7AI gene. It is concluded that common polymorphisms of the CYP7A1 gene do not contribute to variation in cholesterol 7alpha-hydroxylase activity, rates of bile acid synthesis and plasma LDL cholesterol concentration in humans.
Asunto(s)
Ácidos y Sales Biliares/biosíntesis , Colesterol 7-alfa-Hidroxilasa/genética , Colesterol 7-alfa-Hidroxilasa/metabolismo , LDL-Colesterol/sangre , Polimorfismo de Longitud del Fragmento de Restricción , Carcinoma Hepatocelular , Línea Celular Tumoral , Colestenonas/sangre , Pruebas Genéticas , Variación Genética , Haplotipos , Humanos , Neoplasias Hepáticas , Masculino , Persona de Mediana Edad , Regiones Promotoras Genéticas/genética , Transcripción GenéticaRESUMEN
BACKGROUND: Postoperative nausea and vomiting (PONV) is still common, especially among female patients. Our hypothesis is that coinduction with clonidine reduces the incidence of PONV in adult patients undergoing breast cancer surgery. METHODS: Sixty-eight women premedicated with midazolam were randomly allocated to coinduction with intravenous clonidine (group C) or placebo (group P) in this prospective, double-blind study. Anesthesia was standardized (laryngeal mask airway, fentanyl, propofol, sevoflurane, nitrous oxide, and oxygen). Hemodynamic parameters and the requirements for propofol, sevoflurane, and the postoperative need for ketobemidone were noted. The primary endpoints studied were the number of PONV-free patients and patient satisfaction with respect to PONV. RESULTS: Patients in group C had a significantly reduced need for propofol (P < 0.04) and sevoflurane (P < 0.01) and a reduced early need for ketobemidone (P < 0.04). There were significantly more PONV-free patients in group C compared with group P (20 and 11 of 30, respectively; P < 0.04). The number needed to treat was 3.3 (95% confidence interval, 1.8, 16.9). Intraoperative blood pressure, postoperative heart rate, and postoperative blood pressure were all significantly lower in group C compared with group P, but were not considered to be of clinical importance. No negative side effects were recorded. CONCLUSION: Coinduction with clonidine significantly increased the number of PONV-free patients after breast cancer surgery with general anesthesia.