Genotyping the human UDP-glucuronosyl transferase 1 (UGT1) gene

Abstract

Genetic polymorphisms are identified in the human UGT1 gene that alter UGT1-dependent drug metabolism. Nucleic acids comprising the polymorphic sequences are used to screen patients for altered metabolism for UGT1 substrates, potential drug-drug interactions, and adverse/side effects, as well as diseases that result from environmental or occupational exposure to toxins. The nucleic acids are used to establish animal, cell and in vitro models for drug metabolism.

What is claimed is:  
     
         1 . An isolated nucleic acid molecule comprising a UGT1 sequence polymorphism of SEQ ID NOS: 87-124, as part of other than a naturally occurring chromosome.  
     
     
         2 . A nucleic acid probe for detection of UGT1 locus polymorphisms, comprising a polymorphic sequence of SEQ ID NOS:87-124.  
     
     
         3 . A nucleic acid probe according to  claim 2 , wherein said probe is conjugated to a detectable marker.  
     
     
         4 . An array of oligonucleotides comprising: 
 two or more probes for detection of UGT1 locus polymorphisms, said probes comprising at least one form of a polymorphic sequences of SEQ ID NOS:87-124.    
     
     
         5 . A method for detecting in an individual a polymorphism in UGT1 metabolism of a substrate, the method comprising: 
 analyzing the genome of said individual for the presence of at least one UGT1 polymorphism of SEQ ID NOS:87-124; wherein the presence of said predisposing polymorphism is indicative of an alteration in UGT1 expression or activity.    
     
     
         6 . A method according to  claim 5 , wherein said analyzing step comprises detection of specific binding between the genomic DNA of said individual with an array of oligonucleotides comprising: 
 two or more probes for detection of UGT1 locus polymorphisms, said probes comprising at least one form of a polymorphic sequence of SEQ ID NOS:87-124.    
     
     
         7 . A method according to  claim 5 , wherein said alteration in UGT1 expression is tissue specific.  
     
     
         8 . A method according to  claim 5 , wherein said alteration in UGT1 expression is in response to a UGT1 modifier.  
     
     
         9 . A method according to  claim 8 , wherein said modifier induces UGT1 expression.  
     
     
         10 . A method according to  claim 8 , wherein said modifier inhibits UGT1 expression.