Limited influence of UGT1A1*28 and no effect of UGT2B7*2 polymorphisms on UGT1A1 or UGT2B7 activities and protein expression in human liver microsomes

摘要

What is already known about this subject class="unordered" style="list-style-type:disc">The UGT1A1*28 polymorphism is known to reduce UGT1A1 enzyme activities, via an extra TA repeat in the promoter.However, a gap exists with regard to a comprehensive assessment of the influence of this genotype on variability in enzyme activity.There is equivocal evidence on the functional relevance of the UGT2B7*2 polymorphism on UGT2B7 enzyme activities.What this study adds class="unordered" style="list-style-type:disc">Using comprehensive approaches to measure enzyme activities and protein expression levels, the UGT1A1*28 polymorphism is shown to contribute to only 40% of the variability in enzyme activities for UGT1A1.A novel, nonproprietary method for genotyping UGT1A1*28 is provided.Definitive evidence is provided to conclude there is no effect of the UGT2B7*2 polymorphism on zidovudine glucuronidation activity.AimsUGT1A1 and UGT2B7 are enzymes that commonly contribute to drug glucuronidation. Since genetic factors have been suggested to contribute to variability in activities and expression levels of these enzymes, a quantitative assessment of the influence of the major genotypes (UGT1A1*28 or UGT2B7*2) on enzyme activities was conducted.