RESUMEN
The ATP-binding cassette G2 (ABCG2) c.421C>A (rs2231142) polymorphism influences the pharmacokinetics of rosuvastatin. We examined whether this polymorphism influences the low-density lipoprotein cholesterol (LDL-C)-lowering efficacy of the drug. In 305 Chinese patients with hypercholesterolemia who were treated with rosuvastatin at a dosage of 10 mg daily, the c.421A variant was found to be significantly associated with greater reduction in LDL-C level, in a gene-dose-dependent manner. As compared with subjects with the c.421CC genotype, those with the c.421AA genotype showed a 6.9% greater reduction in LDL-C level, which would be equivalent to the effect obtained by doubling the dose of rosuvastatin.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , LDL-Colesterol/sangre , Fluorobencenos/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Hipercolesterolemia/genética , Proteínas de Neoplasias/genética , Polimorfismo de Nucleótido Simple/genética , Pirimidinas/uso terapéutico , Sulfonamidas/uso terapéutico , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Adulto , Anciano , Pueblo Asiatico/genética , LDL-Colesterol/genética , Método Doble Ciego , Femenino , Fluorobencenos/farmacocinética , Estudios de Seguimiento , Humanos , Hipercolesterolemia/sangre , Masculino , Persona de Mediana Edad , Pirimidinas/farmacocinética , Rosuvastatina Cálcica , Sulfonamidas/farmacocinéticaRESUMEN
AIMS/HYPOTHESIS: The transcription factor upstream stimulatory factor 1 (USF1) regulates the expression of genes involved in glucose and lipid metabolism and has been associated with familial combined hyperlipidaemia. USF1 is located on chromosome 1q22-23, a region with evidence for linkage to type 2 diabetes and various traits of the metabolic syndrome in Chinese and other populations. The aim of this study was to investigate the linkage and association of USF1 with type 2 diabetes and the metabolic syndrome in Chinese individuals. MATERIALS AND METHODS: We genotyped three haplotype-tagging single nucleotide polymorphisms (SNPs) (rs3737787, rs2516841 and rs2516839) at USF1 in three samples of the Hong Kong Chinese population, including members of 179 families from the Hong Kong Family Diabetes Study, 1,383 hospital cases with type 2 diabetes and/or the metabolic syndrome and 454 normal control subjects. RESULTS: We found significant association of individual polymorphisms and haplotypes with type 2 diabetes and/or metabolic syndrome-related traits in the family samples using either family-based or unrelated normal control subjects. However, these variants could not explain much of the evidence for linkage in this region. Moreover, they were not associated with type 2 diabetes and/or the metabolic syndrome in the hospital cases. CONCLUSIONS/INTERPRETATION: The results are consistent with the hypothesis that variation at USF1 contributes to the risk of type 2 diabetes and the metabolic syndrome in families with strong evidence for linkage in the chromosome 1q region. However, they provide little support for USF1 as the susceptibility locus that generates the observed evidence for linkage at 1q21-25 for type 2 diabetes and/or the metabolic syndrome, and USF1 does not appear to have a major contribution to these phenotypes in the general Chinese population.