Polymorphism in CYP3A4 gene affecting drug metabolizing and uses thereof

Patent metadata

Field	Value
Publication number	US-9441275-B2
Application number	US-201013259514-A
Country	US
Kind code	B2
Filing date	Mar 26, 2010
Priority date	Mar 26, 2009
Publication date	Sep 13, 2016
Grant date	Sep 13, 2016

Abstract

A method for predicting a subject's risk factors for CYP3A4-related disorders includes detecting the allelic status of a SNP in a nucleic acid sample of the subject.

First claim

What is claimed is:

1. A method of administering a statin dose to a human, comprising:
obtaining a nucleic acid-containing test sample from a human, wherein the human is in need of statin therapy;
conducting at least one genotyping assay of the sample so as to obtain at least the genotype data at position rs35599367 of CYP3A4 in the sample, wherein the at least one genotyping assay comprises hybridizing a tagged primer to DNA in the nucleic acid-containing test sample, amplifying the hybridized DNA and detecting the tagged primer;
detecting a T allele at position rs35599367 of CYP3A4; and
administering a statin dose to the human comprising a TT or TC genotype at position rs35599367 of CYP3A4 of less than 20 mg per day wherein the statin administered is a statin that depends on CYP3A4 for elimination.

2. The method of claim 1 , which further comprises a step of predicting cholesterol control outcome.

3. The method of claim 1 , which further comprises identifying at least one additional biomarker of statin metabolism.

4. The method of claim 1 , wherein said nucleic acid is a nucleic acid extract from a biological sample from said human.

5. The method of claim 4 , in which said sample is blood, saliva, or buccal cells.

6. A method of administering a statin dose to a human, comprising:
obtaining a nucleic acid-containing test sample from a human, wherein the human is in need of statin therapy;
conducting at least one genotyping assay of the sample so as to obtain at least the genotype data at position rs35599367 of CYP3A4 in the sample, wherein the at least one genotyping assay comprises hybridizing a tagged primer to DNA in the nucleic acid-containing test sample, amplifying the hybridized DNA, and detecting the tagged primer;
detecting a C allele at position rs35599367 of CYP3A4; and
administering a statin dose to the human comprising a CC genotype at position rs35599367 of CYP3A4 of more than 40 mg per day, wherein the statin administered is a statin that depends on CYP3A4 for elimination.

7. The method of claim 6 , which further comprises a step of predicting cholesterol control outcome.

8. The method of claim 6 , which further comprises identifying at least one additional biomarker of statin metabolism.

9. The method of claim 6 , wherein said nucleic acid is a nucleic acid extract from a biological sample from said human.

10. The method of claim 9 , in which said sample is blood, saliva, or buccal cells.

11. The method of claim 1 , wherein one or more statins are given, and the one or more statins is selected from the group consisting of atorvastatin, lovastatin, and simvastatin.

12. The method of claim 6 , wherein one or more statins are given, and the one or more statins is selected from the group consisting of atorvastatin, lovastatin, and simvastatin.

Assignees

• Sadee Wolfgang
• Wang Danxin
• Ohio State Innovation Foundation

Inventors

• Sadee Wolfgang
• Wang Danxin

Classifications

• C12Q2600/16

  Primer sets for multiplex assays · CPC title

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title

• C12Q1/6883 Primary

  for diseases caused by alterations of genetic material · CPC title

• G01N2800/044

  Hyperlipemia or hypolipemia, e.g. dyslipidaemia, obesity · CPC title

• G01N33/5038

  involving detection of metabolites per se · CPC title