RESUMO
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.
Assuntos
Dissonias/genética , Sono/genética , Adulto , Negro ou Afro-Americano/genética , Idoso , Feminino , Estudos de Associação Genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Autorrelato , População Branca/genéticaAssuntos
Variação Genética , Oxigenases de Função Mista/genética , Trombose/genética , Trombose Venosa/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Artérias/patologia , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Resultado do Tratamento , Vitamina K Epóxido RedutasesRESUMO
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.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Piridinas/efeitos adversos , Ticlopidina/análogos & derivados , Sistemas de Notificação de Reações Adversas a Medicamentos , Idoso , Idoso de 80 Anos ou mais , Hidrocarboneto de Aril Hidroxilases/antagonistas & inibidores , Estudos de Casos e Controles , Clopidogrel , Citocromo P-450 CYP2C8 , Citocromo P-450 CYP3A , Inibidores do Citocromo P-450 CYP3A , Interações Medicamentosas , Feminino , Humanos , Masculino , Piridinas/metabolismo , Rabdomiólise/induzido quimicamente , Ticlopidina/efeitos adversosRESUMO
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.