Background Information for UDP Glucuronosyltransferase 1A1 
(UGT1A1) Genotyping:

Characteristics: UGT1A1 is responsible for the clearance of drugs 
(e.g., irinotecan) and endbiotic compounds (e.g., bilirubin).  
Irinotecan's major active and toxic metabolite (SN-38) is inactivated 
by UGT1A1 and then eliminated via the bile.  UGT1A1 gene mutations 
cause accumulation of SN-38, which may lead to irinotecan-related 
toxicities (neutropenia, diarrhea).

Cause: Variations in TA repeat number in the TATAAA element of the 5' 
UGT1A1-promoter affects transcription efficiency.  The common number of 
repeats is six [(TA) 6, *1 allele], while seven repeats [(TA) 7, *28 
allele] is associated with reduced transcription activity.  
Homozygosity for the (TA) 7 allele is also associated with Gilbert's 
syndrome (benign familial hyperbilirubinemia).

Alleles detected: *36 allele, (TA)5; *1 allele, (TA)6; *28 allele, (TA)
7 and *37 allele, (TA)8.

Clinical Sensitivity/Specificity: The risk of irinotecan toxicity by 
genotype is shown below (based on data from (Br J Cancer (2004) 
91:678-82).
    TA genotype          Diarrhea      Neutropenia
      6/6  (*1/*1)          17%            15%
      6/7  (*1/*28)         33%            27%
      7/7  (*28/*28)        70%            40%

Allelic Frequency:
  *1 (TA)6: Caucasians - 61%; Asians - 84%; African Americans - 47%
 *28 (TA)7: Caucasians - 39%; Asians - 16%; African Americans - 43%

Analytical Sensitivity: Greater than 99 percent