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Mol Diagn Ther. 2013 Aug;17(4):233-7. doi: 10.1007/s40291-013-0031-x.

UGT1A1*28 is associated with decreased systemic exposure of atorvastatin lactone.

Author information

1
Department of Medical Biochemistry, Oslo University Hospital, University of Oslo, Nydalen, P.O. Box 4956, 0424, Oslo, Norway. camilla.stormo@medisin.uio.no

Abstract

BACKGROUND:

Atorvastatin is commonly used to reduce cholesterol. Atorvastatin acid is converted to its corresponding lactone form spontaneously or via glucuronidation mediated by uridine diphosphate glucuronosyltransferase (UGT) 1A1 and 1A3. Atorvastatin lactone is pharmacologically inactive, but is suspected to be muscle toxic and cause statin-induced myopathy (SIM). A several fold increase in systemic exposure of atorvastatin lactone has previously been observed in patients with SIM compared with healthy control subjects. In this study we aimed to investigate the association between polymorphisms in the UGT1A gene locus and plasma atorvastatin lactone levels.

METHODS:

DNA was extracted from whole blood obtained from a previous pharmacokinetic study of patients carefully diagnosed as having true SIM (n = 13) and healthy control subjects (n = 15). The UGT1A1*28(TA) 7 , UGT1A3*2, UGT1A3*3, and UGT1A3*6 polymorphisms were detected by pyrosequencing.

RESULTS:

Carriers of the low-expression allele UGT1A1*28(TA) 7 tended to have lower levels of atorvastatin lactone (p < 0.05) than carriers with the normal-activity allele (TA) 6 .

CONCLUSION:

The low-expression UGT1A1*28(TA) 7 allele seems to be associated with decreased systemic exposure of the suspected muscle-toxic metabolite atorvastatin lactone.

PMID:
23580084
DOI:
10.1007/s40291-013-0031-x
[Indexed for MEDLINE]

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