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• W2097502023 abstract "Interindividual variability in the glucuronidation of xenobiotics metabolized by UDP-glucuronosyltransferase 1A9 (UGT1A9) suggests the presence of functional <i>UGT1A9</i> variants. The aim of this study was to evaluate whether the putative functionality of the <i>UGT1A9</i> variants–<i>118T₉</i>_><i>₁₀</i> (rs3832043), <i>I399C</i>><i>T</i> (rs2741049), –<i>275T</i>><i>A</i> (rs6714486), and–<i>2152C</i>><i>T</i> (rs17868320) could be confirmed in an independent study. <i>UGT1A9</i> genotypes and UGT1A9 activity (i.e., flavopiridol and mycophenolic acid glucuronidation) were determined in 46 Caucasian human livers. mRNA levels were quantitated by real-time polymerase chain reaction in 35 of these livers. In addition, samples from 60 unrelated Caucasians belonging to the HapMap Project were also genotyped to confirm the allele frequencies and linkage disequilibrium (LD) pattern observed in our Caucasian livers. The allele frequencies of the–<i>118T₉</i>_>10, <i>I399C</i>><i>T</i>, –<i>275T</i>><i>A, </i> and–<i>2152C</i>><i>T</i> variants were 0.39, 0.39, 0.02, and 0.02 in the livers, respectively. The <i>I399C</i>><i>T</i> variant was in complete LD (<i>r</i>² = 1) with–<i>118T₉</i>_><i>₁₀</i> (linked alleles: C and T₉, respectively). Complete LD between these two variants was also found in the HapMap samples (frequencies of–<i>118T₉</i>_><i>₁₀</i> and <i>I399C</i>><i>T</i> = 0.38). <i>I399C</i>><i>T</i> and–<i>118T₉</i>_><i>₁₀</i> correlated with neither UGT1A9 activities nor mRNA levels. Because of the low frequencies of the–<i>275T</i>><i>A</i> and–<i>2152C</i>><i>T</i> variants, an effect on phenotype could not be evaluated. Our data demonstrate that the common <i>I399C</i>><i>T</i> and–<i>118T₉</i>_><i>₁₀</i> polymorphisms do not explain interindividual variation in hepatic UGT1A9 activity and mRNA expression and are in complete LD in the donor liver samples we studied." @default.
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• W2097502023 date "2007-08-30" @default.
• W2097502023 modified "2023-10-10" @default.
• W2097502023 title "Lack of Association between Common Polymorphisms in UGT1A9 and Gene Expression and Activity" @default.
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• W2097502023 doi "https://doi.org/10.1124/dmd.107.015446" @default.
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