RESUMEN
Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.
Asunto(s)
Disomnias/genética , Sueño/genética , Adulto , Negro o Afroamericano/genética , Anciano , Femenino , Estudios de Asociación Genética , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Autoinforme , Población Blanca/genéticaAsunto(s)
Variación Genética , Oxigenasas de Función Mixta/genética , Trombosis/genética , Trombosis de la Vena/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Arterias/patología , Femenino , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Resultado del Tratamiento , Vitamina K Epóxido ReductasasRESUMEN
An analysis of a case-control study of rhabdomyolysis was conducted to screen for previously unrecognized cytochrome P450 enzyme (CYP) 2C8 inhibitors that may cause other clinically important drug-drug interactions. Medication use in cases of rhabdomyolysis using cerivastatin (n = 72) was compared with that in controls using atorvastatin (n = 287) for the period 1998-2001. The use of clopidogrel was strongly associated with rhabdomyolysis (odds ratio (OR) 29.6; 95% confidence interval (CI), 6.1-143). In a replication effort that used the US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS), it was found that clopidogrel was used more commonly in patients with rhabdomyolysis receiving cerivastatin (17%) than in those receiving atorvastatin (0%, OR infinity; 95% CI = 5.2-infinity). Several medications were tested in vitro for their potential to cause drug-drug interactions. Clopidogrel, rosiglitazone, and montelukast were the most potent inhibitors of cerivastatin metabolism. Clopidogrel and its metabolites also inhibited cerivastatin metabolism in human hepatocytes. These epidemiological and in vitro findings suggest that clopidogrel may cause clinically important, dose-dependent drug-drug interactions with other medications metabolized by CYP2C8.
Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Piridinas/efectos adversos , Ticlopidina/análogos & derivados , Sistemas de Registro de Reacción Adversa a Medicamentos , Anciano , Anciano de 80 o más Años , Hidrocarburo de Aril Hidroxilasas/antagonistas & inhibidores , Estudios de Casos y Controles , Clopidogrel , Citocromo P-450 CYP2C8 , Citocromo P-450 CYP3A , Inhibidores del Citocromo P-450 CYP3A , Interacciones Farmacológicas , Femenino , Humanos , Masculino , Piridinas/metabolismo , Rabdomiólisis/inducido químicamente , Ticlopidina/efectos adversosRESUMEN
OBJECTIVES: This study investigated the effect on the risk and cost of unintended pregnancies of emergency contraceptive pills obtained directly from a pharmacist. METHODS: We used a decision model to compare outcomes for private and public payers following unprotected intercourse from. RESULTS: Obtaining emergency contraceptive pills from a pharmacy, compared with obtaining them from a physician or clinic, resulted in a $158 (95% confidence interval (CI) =$76, $269) reduction in costs for private payers and a $48 (95% CI = $16, $93) reduction for public payers. CONCLUSIONS: Our findings suggest that under varied assumptions, obtaining emergency contraceptive pills directly from a pharmacist reduces the number of unintended pregnancies and is cost saving.