Methods for detection of promoter polymorphism in a UGT gene promoter

Abstract

The present invention is directed to methods for detecting the presence of genetic polymorphisms that correlate with altered gene expression. More specifically, the present invention is directed to methods for detecting the genetic polymorphisms located in the UGT1A1 promoter. The invention also provides methods for optimizing drug dosages based upon the presence of the polymorphisms. The invention further provides methods of predicting sensitivity to xenobiotics and diagnostic kits for detecting genetic polymorphisms.

1 .- 66 . (canceled) 
     
     
         67 . A kit for detecting polymorphisms in a uridine diphosphate glucuronosyltransferase I (UGT1A1) gene promoter wherein the number of thymidine-adenine (TA) repeats in said UGT1 gene promoter correlates to expression of said UGT1 gene, the kit comprising primers for amplifying DNA comprising all or part of the UGT1 gene promoter to determine the number of TA repeats in said promoter. 
     
     
         68 . The kit of  claim 67  wherein said kit contains one or more additional components selected from the group consisting of deoxynucleoside triphosphates, buffers, labels for detecting said polymorphisms and instructions. 
     
     
         69 . The kit of  claim 67  wherein the primers are selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 and SEQ ID NO: 4. 
     
     
         70 . A method for reducing irinotecan toxicity in a patient comprising: administering irinotecan to a patient whose genotype has been evaluated for the number of TA repeats in the uridine diphosphate glucuronosyltransferase I (UGT1A1) promoter, wherein a patient with seven or eight TA repeats in at least one allele is given an adjusted amount of irinotecan compared to a patient who does not have seven or eight TA repeats. 
     
     
         71 . A method comprising administering irinotecan to a cancer patient who was previously evaluated for the number of (TA) repeats in the uridine diphosphate glucuronosyl transferase A1 (UGTA1) gene promoter of the patient based on a sample from the patient. 
     
     
         72 . The method of  claim 71 , wherein the patient has five or six TA repeats. 
     
     
         73 . The method of  claim 72 , wherein the patient has five TA repeats. 
     
     
         74 . The method of  claim 71 , wherein the patient has seven repeats and/or eight repeats and is administered a dosage of irinotecan that is less than the amount the patient would have been given if the patient did not have seven and/or eight repeats.