Genetic polymorphisms in the human HMG-CoA reductase gene and their use in diagnosis and treatment of diseases
AssigneeAstraZeneca UK Limited, a English corporation
InventorsRuth E. March, Sarah M. Thornton
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Abstract
This invention relates to polymorphisms in the human HMG-CoA reductase gene and corresponding novel allelic polypeptides encoded thereby. Particular polymorphisms are described in the promoter, exon 15 and introns 2, 5, 15 and 18. The invention also relates to methods and materials for analysing allelic variation in the HMG CoA reductase gene, and to the use of HMG-CoA reductase polymorphism in the diagnosis and treatment of HMG-CoA reductase mediated diseases such as dyslipidemia and other cardiovascular diseases such as myocardial infarction and stroke.
Claims12
A method for the diagnosis of a single nucleotide polymorphism in HMG-CoA reductase in a human, which method comprises determining the sequence of the nucleic acid of the human at at least one polymorphic position selected from one or more of the following positions:
- position 1962 in the coding sequence of the HMG-CoA reductase gene as defined by the position in SEQ ID NO:
- 44, and/or
- positions 46 or 267 in the promoter sequence of the HMG-CoA reductase gene as defined by the positions in SEQ ID NO:
- 45;
- and/or
- position 129 in intron 2 as defined by the position in SEQ ID NO:20, and/or
- position 550 in intron 5 as defined by the position in SEQ ID NO:
- 24, and/or
- position 37 in intron 15 as defined by the position in SEQ ID NO:37, and/or
- position 345 in intron 18 as defined by the position in SEQ ID NO:40 of the HMG-CoA reductase gene, and
- determining the status of the human by reference to polymorphism in the HMG-CoA reductase gene.
An isolated polynucleotide comprising at least 20 bases of the human HMG-CoA reductase gene and comprising a polymorphism selected from any one of the following:
- 15 Region SEQ ID Position Polymorphism Exon 15 SEQ ID NO:
- 44 1962 A → G promoter SEQ ID NO:
- 45 46 C → G promoter SEQ ID NO:
- 45 267 T → C Intron 2 SEQ ID NO:
- 20 129 CT → CAAT Intron 5 SEQ ID NO:
- 24 550 T → A Intron 15 SEQ ID NO:
- 37 37 A → G Intron 18 SEQ ID NO:
- 40 345 T → C
9 A computer readable medium comprising at least one polymorphism as defined in the table of claim 6 stored on the medium.
10 A method of treating a human in need of treatment with a HMG-CoA reductase inhibitor drug in which the method comprises:
- i) diagnosis of a single nucleotide polymorphism in HMG-CoA reductase gene in the human, which diagnosis comprises determining the sequence of the nucleic acid at one or more of the following positions:
- position 1962 in the coding sequence of the HMG-CoA reductase gene as defined by the position in SEQ ID NO:
- 44, and/or
- positions 46 or 267 in the promoter sequence of the HMG-CoA reductase gene as defined by the positions in SEQ ID NO:
- 45;
- and/or
- position 129 in intron 2 as defined by the position in SEQ ID NO:20, and/or
- position 550 in intron 5 as defined by the position in SEQ ID NO:
- 24, and/or
- position 37 in intron 15 as defined by the position in SEQ ID NO:37, and/or
- position 345 in intron 18 as defined by the position in SEQ ID NO:40 of the HMG-CoA reductase gene,
- and determining the status of the human by reference to polymorphism in the HMG-CoA reductase gene;
- and
- ii) administering an effective amount of a HMG-CoA reductase inhibitor.
11 An allelic variant of human HMG-CoA reductase polypeptide comprising a valine at position 638 or a fragment thereof comprising at least 10 amino acids provided that the fragment comprises the valine at position 638.
12 A polynucleotide sequence comprising any one of the intron sequences of HMG-CoA reductase defined in any one of SEQ ID NOS:
- 18-41 and 54 or a complementary strand thereof or a sequence at least 90% homologous thereto.
Dependencies are inferred from the claim text.