Genotyping human UDP-Glucuronsyltransferase 2B15 (UGT2B15) genes

Abstract

Genetic polymorphisms are identified in the human UGT2B4, UGT2B7 and UGT2B15 genes that alter UGT2B activity. Nucleic acids comprising the polymorphic sequences are used to screen patients for altered metabolism for UGT2B 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 UGT2B sequence polymorphism of SEQ ID NOs:25-38; 84-111 or 147-164, as part of other than a naturally occurring chromosome.  
     
     
         2 . A nucleic acid probe for detection of UGT2B locus polymorphisms, comprising a polymorphic sequence of SEQ ID NOs:25-38; 84-111 or 147-164.  
     
     
         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 UGT2B locus polymorphisms, said probes comprising at least one form of a polymorphic sequences of SEQ ID NOs:25-38; 84-111 is or 147-164.    
     
     
         5 . A method for detecting in an individual a polymorphism in a UGT2B metabolism of a substrate, the method comprising: 
 analyzing the genome of said individual for the presence of at least one UGT2B polymorphism of SEQ ID NOs:25-38; 84-111 or 147-164; wherein the presence of said predisposing polymorphism is indicative of an alteration in UGT2B 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 UGT2B locus polymorphisms, said probes comprising at least one form of a polymorphic sequence of SEQ ID NOs:25-38; 84-111 or 147-164.    
     
     
         7 . A method according to  claim 5 , wherein said alteration in UGT2B expression is tissue specific.  
     
     
         8 . A method according to  claim 5 , wherein said alteration in UGT2B expression is in response to a UGT2B modifier.  
     
     
         9 . A method according to  claim 8 , wherein said modifier induces UGT2B expression.  
     
     
         10 . A method according to  claim 8 , wherein said modifier inhibits UGT2B expression.