Polymorphisms in the human CYP2D6 gene promoter region and their use in diagnostic and therapeutic applications
View Patent ↗Provided are polynucleotides of molecular variant promoters of the CYP2D6 gene which, for example, are associated with abnormal drug response or individual predisposition to several common diseases and disorders caused by drug under- or over-metabolization, and vectors comprising such polynucleotides. Furthermore, methods of diagnosing the status of disorders related to intermediate metabolization of drugs are described. In addition, kits comprising oligonucleotides hybridizing to the CYP2D6 promoter and/or being capable of being extended into this region useful for diagnosing subjects that are ultrarapid or intermediate metabolizer of drugs are provided.
1. A method of identifying a human subject as being at risk for reduced CYP2D6 activity, comprising:
(a) detecting in vitro in a sample from the human subject the CYP2D6 genotype at position 36 of SEQ ID NO: 1; and
(b) identifying the human subject having a homozygous Cytosine (C) at position 36 of SEQ ID NO: 1 as having risk for reduced CYP2D6 activity relative to a human subject having a heterozygous or homozygous Guanine (G) at position 36 of SEQ ID NO: 1.
2. The method of claim 1 wherein detection is performed using at least one of polymerase chain reaction (PCR), ligase chain reaction, restriction digestion, direct sequencing, nucleic acid amplification techniques and hybridization techniques.
3. The method of claim 1 , wherein the detecting step utilizes polymerase chain reaction (PCR).
4. The method of claim 1 , wherein the detecting step utilizes a nucleic acid molecule of 15-50 nucleotides that hybridizes to a polynucleotide comprising a C at position 36 of SEQ ID NO: 1.
5. The method of claim 3 , wherein the PCR product comprises a C at position 36 of SEQ ID NO: 1.
6. A method of identifying a human subject as being at risk for reduced CYP2D6 activity, comprising:
(a) detecting in vitro in a sample from the human subject the nucleotide at polymorphic site −1584 of the CYP2D6 gene promoter, which is position 36 of SEQ ID NO: 1, and
(b) identifying the human subject having a homozygous Cytosine (C) at said polymorphic site -1584 of the CYP2D6 gene promoter as having risk for reduced CYP2D6 activity relative to a human subject having a heterozygous or homozygous Guanine (G) at said polymorphic site.
7. The method of claim 6 , wherein detection is performed using at least one of polymerase chain reaction (PCR), ligase chain reaction, restriction digestion, direct sequencing, nucleic acid amplification techniques and hybridization techniques.
8. The method of claim 6 , wherein the detecting step utilizes polymerase chain reaction (PCR).
9. The method of claim 6 , wherein the detecting step utilizes a nucleic acid molecule of 15-50 nucleotides that hybridizes to a polynucleotide comprising a C at position 36 of SEQ ID NO: 1.
10. The method of claim 8 , wherein the PCR product comprises a C at position 36 of SEQ ID NO: 1 or the complement thereof.