Diagnostic methods

• US 8,455,194 B2
• Filed: 02/29/2012
• Issued: 06/04/2013
• Est. Priority Date: 02/29/2008
• Status: Active Grant

• Current Assignee: Oxford University Innovation Limited (University of Oxford)
• Original Assignee: Isis Innovation Limited
• Inventors: Link, Emma, Parish, Sarah, Collins, Rory, Lathrop, Mark
• Primary Examiner(s): SITTON, JEHANNE SOUAYA
• Application Number:
  US13/408,672
• Publication Number:
  US 20120202205A1
• Time in Patent Office: 461 Days
• Field of Search: None
• US Class Current: 435/6.1
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C12Q 1/6876 Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/172 Haplotypes

Abstract

This invention relates to a method of determining the susceptibility of an individual to statin-induced myopathy, comprising detecting the presence or absence of one or more polymorphisms in the SLCO1B1 gene in a biological sample from an individual, whereby the presence of one or more polymorphisms indicates that the individual has altered susceptibility to statin-induced myopathy.

Claims

1. A method, comprising:

(a) assaying for the presence or absence of a C or T allele for single nucleotide polymorphism rs4149056 in the SLCO1B1 gene in a biological sample obtained from a patient in need of treatment with a statin;

(b) correlating the identity of the allele of said polymorphism with risk of statin-induced myopathy;

(c) establishing a statin type and dosage based on said patient'"'"'s statin-induced myopathy risk; and

(d) administering said statin type and dosage to said patient.

2. The method of claim 1, wherein said assaying step comprises amplifying at least part of the SLCO1B1 gene comprising said polymorphism, and identifying the nucleotide present in at least one allele of said polymorphism in the amplified gene.

3. The method of claim 2, wherein said assaying step comprises amplifying exon 6 of the SLCO1B1 gene comprising the SNP rs4149056.

4. The method of claim 1, wherein said biological sample is selected from the group consisting of individual cells, cell populations, bodily tissues, and bodily fluids.

5. The method of claim 1, wherein, for a patient with the TT genotype, said administered statin dosage is higher than the standard dosage, and for a patient with a CC or TC genotype, said statin dosage is the standard dosage.

6. The method of claim 1, wherein said statin is lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, pitayastatin, or rosuvastatin.

7. The method of claim 6, wherein said statin is atorvastatin or simvastatin.

8. A method comprising:

(a) assaying for the presence of a C or T allele for single nucleotide polymorphism rs4363657 in the SLCO1B1 gene in a biological sample obtained from a patient in need of treatment with a statin;

(b) correlating the identity of the allele of said polymorphism with risk of statininduced myopathy;

(c) establishing a statin type and dosage based on said patient'"'"'s statin-induced myopathy risk; and

(d) administering said statin type and dosage to said patient.

9. The method of claim 8, wherein said assaying step comprises amplifying at least part of the SLCO1B1 gene comprising said polymorphism, and identifying the nucleotide present in at least one allele of said polymorphism in the amplified gene.

10. The method of claim 9, wherein said assaying step comprises amplifying intron 11 of the SLCO1B1 gene comprising the SNP rs4363657.

11. The method of claim 8, wherein said biological sample is selected from the group consisting of individual cells, cell populations, bodily tissues, and bodily fluids.

12. The method of claim 8, wherein, for a patient with the IT genotype, said administered statin dosage is higher than the standard dosage, and for a patient with a CC or IC genotype, said statin dosage is the standard dosage.

13. The method of claim 8, wherein said statin is lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, pitavastatin, or rosuvastatin.

14. The method of claim 13, wherein said statin is atorvastatin or simvastatin.