Farmacogenetics and adverse reaction to drugs

Predictive value of polymorphism in the uridine diphosphate glucoronosyltransferase 1A1 gene

Abstract

Introduction: adverse reactions to drugs constitute an essential problem for health services, the pharmaceutical industry and the regulatory bodies. Most of these reactions are relatively mild and they disappear when dosage is modified, although others are more serious and they may result in death. Irinotecan is an active cytotoxic agent in colorectal and lung cancer. It is associated to severe hematological and gastrointestinal toxicity, unpredictable in practice. Its active metabolite (SN-38) is detoxified by the uridine diphosphate glucoronosyltransferase 1A1enzyme (UGT1A1). (UGT1A1). Variation in the activity of this enzyme has been associated to polymorphisms in the UGT1A1 gene, what results in the adverse reactions observed. The most important polymorphisms appear in the polymorphism of the promoting region, which consists in a variable repetition of thymine-adenine repetitions. The main allele has six repetitions (TA)6, being the seven repetition polymorphism the most frequent allelic variant.
Objetive: to design a molecular test to study allelic variants of the promoting region in the UGT1A1 gene.
Method: We selected a group of 50 volunteers with no family bonds. Amplification and subsequent sequencing of the promoting region were used to determine molecules.
Results: we managed to update the suggested molecular diagnosis and determined that 8% of this population is a homozygote (TA)7. We propose the advantage of incorporating the results of this molecular test for the making of therapeutic decisions and thus make progress toward a more personalized oncologic medicine.