Tolerability of statins is not linked to CYP450 polymorphisms, but reduced CYP2D6 metabolism improves cholesteraemic response to simvastatin and fluvastatin

Zuccaro, Piergiorgio; Mombelli, Giuliana; Calabresi, Laura; Baldassarre, Damiano; Palmi, Ilaria; Sirtori, Cesare R.

doi:10.1016/j.phrs.2006.12.009

Cited by 69 publications

(30 citation statements)

References 47 publications

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“…those who were not prescribed atorvastatin therapy), 28% of individuals expressed the CYP2D6*4 polymorphism [20]. In a study of ours we noted the highest efficacy of the statin in the CYP2D6*1/4* and *4/4* PM patients, but we have not observed an increase of ADRs in carriers of PM [21].…”

Section: Variants Of Cyp450contrasting

confidence: 56%

Statin Muscle Toxicity and Genetic Risk Factors

Mombelli¹

2013

Int J Genomic Med

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Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) can cause skeletal muscle toxicity; the risk of toxicity is elevated by drug interactions and pharmacogenetic factors that increase the concentration of statins in plasma.The genetic basis of statin-related muscle disorders is largely unknown. Statins are substrates for several membrane transporters that may mediate drug interactions. Potent inhibitors of cytochrome P450 (CYP450) especially CYP3A4, can significantly increase the plasma concentrations of the active forms of atorvastatin, lovastatin and simvastatin. Fluvastatin, which is metabolized by CYP2C9, is less prone to pharmacokinetic interactions, while pravastatin and rosuvastatin are not susceptible to any CYP inhibition. OATP1B1 can decrease the hepatic uptake of many statins, as well as the therapeutic index of these agents. Polymorphisms of CYP450 enzymes, SLCO1B1, ABCB1, and COQ2 gene, can induce statin intolerance. This review summarized the principal relations known between statin myotoxicity and genetic risk factors.

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Section: Variants Of Cyp450contrasting

confidence: 56%

Statin Muscle Toxicity and Genetic Risk Factors

Mombelli¹

2013

Int J Genomic Med

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“…53,85,87,91,95,101,107,112 114,116,125 However, in studies conducted among Asians, e4 carriers were associated with a greater response, followed by the e2 carriers and e3 homozygotes ( Table 3.2). 118,122,124,125 In addition, in Asians, e2 carriers and e3e3 homozygotes had poorer responses than did Caucasians, indicating that ethnicity might mediate the association between Apo E and response to statin therapy.…”

Section: Ethnicitymentioning

confidence: 99%

“…83,85,95,100,101,107,[112][113][114]116,118,122,124,125 In the familial hyperlipidemia studies, the e2 allele was associated with the greatest response among the genetic subgroups. The e3e3 homozygotes had greater reductions in TC than did the e4 carriers.…”

Section: Familial Hyperlipidemiamentioning

confidence: 99%

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Horizon scanning for new genomic tests

Gwinn

Grossniklaus

et al. 2011

Genetics in Medicine

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“…Data from 24 studies published in 20 articles that investigated the association between APOE genotypes and statin therapy met the inclusion criteria. [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Two articles provided separate data for gender or statin dose. 15,24 Figure 1 presents a flowchart of retrieved and excluded studies, with the reasons for exclusion.…”

Section: Eligible Studiesmentioning

confidence: 99%

APOE gene polymorphisms and response to statin therapy

et al. 2009

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Published studies investigating the role of APOE gene on lipid response (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides) to statin treatment have reported inconsistent results. A meta-analysis was conducted to estimate the lipid response to statin treatment among APOE genetic variants (e2 carriers, e3e3 homozygotes and e4 carriers). Twenty-four studies were included in the meta-analyses. The pooled mean reduction (Dm) in TC from baseline was significant for all variants (e2 carriers: Dm ¼ À27.7% (À32.5 to À22.8%), e3e3: Dm ¼ À25.3% (À28.0 to À22.6%) and e4 carriers: Dm ¼ À25.1% (À29.3 to À21.0%)). Significant changes in LDL-C, HDL-C and triglyceride levels were also noted for all genotypes, although these changes did not differ significantly among genotypic groups. There was significant heterogeneity among the studies. Given these non-significant effects of APOE genotypes on lipid responses, there is little reason to consider the use of APOE genetic testing for guiding treatment with statins.

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Tolerability of statins is not linked to CYP450 polymorphisms, but reduced CYP2D6 metabolism improves cholesteraemic response to simvastatin and fluvastatin

Cited by 69 publications

References 47 publications

Statin Muscle Toxicity and Genetic Risk Factors

Statin Muscle Toxicity and Genetic Risk Factors

Horizon scanning for new genomic tests

APOE gene polymorphisms and response to statin therapy

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