PMID- 17289397
OWN - NLM
STAT- MEDLINE
DCOM- 20070829
LR  - 20181201
IS  - 1043-6618 (Print)
IS  - 1043-6618 (Linking)
VI  - 55
IP  - 4
DP  - 2007 Apr
TI  - Tolerability of statins is not linked to CYP450 polymorphisms, but reduced CYP2D6 
      metabolism improves cholesteraemic response to simvastatin and fluvastatin.
PG  - 310-7
AB  - Statin therapy, although generally well tolerated, leads not infrequently to 
      significant subjective and at times objective adverse effects (AEs), mainly of a 
      muscular nature. The genetic background of these AEs is not clear and possibly 
      side effects and lipid lowering efficacy may be linked. Aim of the study was a 
      detailed evaluation of CYP450 and apolipoprotein E gene polymorphisms in two 
      large series of age-sex matched patients with and without muscular side effects 
      to statins. In a Clinical Institution specialised in lipid-lipoprotein disorders, 
      50 statin treated patients were selected, with subjective or objective 
      statin-associated myopathy, evaluated using standardized forms. These were sex 
      and age matched with 50 statin-treated patients from the same Clinic, without any 
      subjective or objective complaints. DNA samples for the evaluation of CYP450 
      genetic polymorphisms and apo E genotypes were collected in order to assess 
      correlations with both genetic polymorphisms and AEs, as well as with therapeutic 
      efficacy. None of the assessed CYP450 polymorphisms appeared to be related to an 
      increased incidence of AEs. The CYP2D6 *1/*4 and *4/4* poor metabolizer (PM) 
      status was associated to a higher efficacy of statins metabolized by this system 
      and, in addition, the apo E2 genotype was, in this series, linked to increased 
      HDL-C levels after therapy. Patients with statin associated myopathy are not 
      characterized by significantly different genotypes for the CYP450s responsible 
      for statin metabolism. On the other hand, CYP2D6 PM status is associated to an 
      increased efficacy of statins metabolized by this system.
FAU - Zuccaro, Piergiorgio
AU  - Zuccaro P
AD  - Department of Drug Research and Evaluation, Italian National Institute of Health, 
      Rome, Italy.
FAU - Mombelli, Giuliana
AU  - Mombelli G
FAU - Calabresi, Laura
AU  - Calabresi L
FAU - Baldassarre, Damiano
AU  - Baldassarre D
FAU - Palmi, Ilaria
AU  - Palmi I
FAU - Sirtori, Cesare R
AU  - Sirtori CR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070114
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Apolipoproteins E)
RN  - 0 (Fatty Acids, Monounsaturated)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Indoles)
RN  - 4L066368AS (Fluvastatin)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - AGG2FN16EV (Simvastatin)
RN  - EC 1.14.13.- (CYP2C9 protein, human)
RN  - EC 1.14.13.- (Cytochrome P-450 CYP2C9)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
RN  - EC 1.14.14.1 (CYP3A5 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2D6)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP3A)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Apolipoproteins E/genetics
MH  - Aryl Hydrocarbon Hydroxylases/genetics
MH  - Case-Control Studies
MH  - Cholesterol/blood
MH  - Cytochrome P-450 CYP2C9
MH  - Cytochrome P-450 CYP2D6/genetics/metabolism
MH  - Cytochrome P-450 CYP3A
MH  - Cytochrome P-450 Enzyme System/*genetics/metabolism
MH  - Fatty Acids, Monounsaturated/*adverse effects/metabolism
MH  - Female
MH  - Fluvastatin
MH  - Gene Frequency
MH  - Genotype
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects/metabolism
MH  - Hypercholesterolemia/*drug therapy/enzymology/genetics
MH  - Indoles/*adverse effects/metabolism
MH  - Male
MH  - Middle Aged
MH  - Muscular Diseases/*chemically induced/enzymology/genetics
MH  - Phenotype
MH  - *Polymorphism, Genetic
MH  - Risk Factors
MH  - Simvastatin/*adverse effects/metabolism
MH  - Treatment Outcome
EDAT- 2007/02/10 09:00
MHDA- 2007/08/30 09:00
CRDT- 2007/02/10 09:00
PHST- 2006/09/25 00:00 [received]
PHST- 2006/12/14 00:00 [revised]
PHST- 2006/12/18 00:00 [accepted]
PHST- 2007/02/10 09:00 [pubmed]
PHST- 2007/08/30 09:00 [medline]
PHST- 2007/02/10 09:00 [entrez]
AID - S1043-6618(07)00013-8 [pii]
AID - 10.1016/j.phrs.2006.12.009 [doi]
PST - ppublish
SO  - Pharmacol Res. 2007 Apr;55(4):310-7. doi: 10.1016/j.phrs.2006.12.009. Epub 2007 
      Jan 14.