Pharmacogenomics of Statin Responsiveness

Efecto de variantes de los genes ABCB1 y CYP3A4 sobre la respuesta terapéutica a atorvastatina en individuos chilenos hipercolesterolémicos

“…A la fecha, se han investigado más de 40 genes que afectan la respuesta a estatinas 10 , relacionados tanto con la farmacocinética (enzimas de metabolización y proteínas de transporte) como con la farmacodinámica del medicamento (receptores y vías de transducción de señal) 11 . Estas variaciones incluyen a genes que actúan en la absorción intestinal de colesterol como la apolipoproteína E (APOE), transportador de ATP (ABC); la producción de colesterol, como la HMG-CoA reductasa; el metabolismo de las lipoproteínas como la apolipoproteína B y el receptor de LDL, como además, de aquellos que actúan en la vía de la citocromo P450 [12][13][14][15] . Las estatinas son metabolizadas por vía hepática, principalmente por la familia de la citocromo P450.…”

Therapeutic potential of statins in multiple sclerosis: immune modulation, neuroprotection and neurorepair

“…The efficacy of different statins varies depending upon their bioavailability governed by their hydrophobicity and their turnover by the cytochrome P450 enzyme system [12]. Secondly, the bioavailability of statins is also affected by polymorphisms in genes coding for ApoE, ABC drug transporters, HMG-CoA reductase and the cytochrome P450 enzyme system [18].…”

Apolipoprotein A-V Genetic Variation and Plasma Lipoprotein Response to Fibrates

“…[1][2][3] In theory, interindividual differences in drug response could be the result of functional polymorphisms in the human genome that encode differences in: (1) gene products that act within pathophysiological pathways underlying the disease whose natural history is being targeted by the drug; (2) pharmacokinetic activity of drug transporters or of processing or metabolizing enzymes; and (3) pharmacodynamics of gene products expressed as carriers or receptors for drug molecules. In the lipoprotein field, inhibitors of 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) (HMG-CoA) reductase ("statins") have been studied pharmacogenetically, with genotypes of many common DNA polymorphisms associated with variation in plasma low-density lipoprotein (LDL) cholesterol responsiveness (reviewed by Kajinami et al 1 ).…”

“…The associated genes typically encode proteins that are involved in cholesterol biosynthesis, such as HMG-CoA reductase, in plasma LDL metabolism, such as the LDL receptor, apolipoprotein (apo) E and B, and in drug metabolism, such as certain cytochrome P450 enzymes. 1 Furthermore, the severity of adverse events from statin treatment, such as myopathy, could be determined in part by interindividual variation in genes involved in ubiquitination. 4 Similarly, plasma LDL cholesterol response to the cholesterol absorption inhibitor ezetimibe has been associated with variation in Niemann-Pick C like protein 1 (NPC1L1), the presumed target of ezetimibe (reviewed by Huff et al 5 ).…”