Haplotype analysis of UGT1A1 and UGT1A9 gene polymorphisms related to the glucuronidation of SN-38, the active metabolite of irinotecan

2085 Background: There are 9 unique UGT1A enzymes with overlapping specificity and tissue-specific expression, which are generated from a single gene by alternative splicing of individual exons 1 with common exons 2–5. The TA repeat polymorphism in UGT1A1and other UGT1A1 variants have been suggested to play a role in increased risk of severe toxicity of irinotecan. In addition to UGT1A1, UGT1A9 enzyme has also been proposed to inactivate SN-38, and a T indel in the 5' untranslated region has been associated with altered gene expression. As UGT1A1-UGT1A9 haplotypes might have a different phenotypic effect compared to single variants, we sought to determine the haplotype map of UGT1A1 and UGT1A9functional variants. Asian (n=150) and Caucasian (n=66) samples were used to evaluate interethnic differences in haplotype structure. Methods: DNA samples were genotyped for variants in UGT1A9 (-11810T/9T) and UGT1A1 [-3279G>T, -3156G>A, -53TA5–8, 211G>A, 686C>A]. Results: In both populations, significant linkage dis...