UGT1A1*28 polymorphism in chronic lymphocytic leukemia: the first investigation of the polymorphism in disease susceptibility and its specific cytogenetic abnormalities
| Autor: | Maria Karakosta, Kalliopi N. Manola, Alkiviadis Kostakis, Gabriel E. Pantelias, Ioannis Rombos, Gregory Kouraklis, Vassiliki Kalotychou |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Chronic lymphocytic leukemia digestive system Pathogenesis chemistry.chemical_compound Downregulation and upregulation Gene Frequency immune system diseases hemic and lymphatic diseases Genotype Genetic predisposition medicine Humans Genetic Predisposition to Disease Glucuronosyltransferase Dinucleotide Repeats In Situ Hybridization Fluorescence Aged Aged 80 and over Polymorphism Genetic medicine.diagnostic_test business.industry UGT1A1*28 polymorphism Hematology General Medicine Middle Aged medicine.disease Prognosis Leukemia Lymphocytic Chronic B-Cell Uridine diphosphate chemistry Case-Control Studies Karyotyping Immunology Female business Fluorescence in situ hybridization |
| Zdroj: | Acta haematologica. 132(1) |
| ISSN: | 1421-9662 |
| Popis: | Chronic lymphocytic leukemia (CLL) has been recently attributed to a combination of genetic predisposition and exposure to environmental factors. UDP-glucuronosyltransferase (UGT)1A1*28 is an inborn polymorphism that results in significant downregulation of uridine diphosphate glucuronyltransferase 1-1 (UGT1A1) activity, one of the most critical metabolizing enzymes involved in the detoxification of toxic substances, some of which contribute to CLL pathogenesis. Here, for the first time, we investigated the putative impact of UGT1A1*28 on CLL incidence and on the formation of the most common chromosomal abnormalities of CLL. UGT1A1*28 was investigated in 109 CLL patients and 108 healthy controls, and was associated with karyotypic and fluorescence in situ hybridization (FISH) results. A significant high frequency of the mutant genotype was observed in patients carrying abnormal FISH patterns, especially del(11q) and +12, which are CLL-specific abnormalities. We also observed a significant association between UGT1A1*28 and the intermediate to unfavorable cytogenetic CLL risk groups. No difference, though, was observed in genotypes between patients and controls. Therefore, we could suggest that UGT-deficient individuals may be at a greater risk for developing CLL-specific abnormalities. Our study might serve as a starting point to consider UGT1A1*28 polymorphism as one of the possible predisposing factors of CLL pathogenesis. |
| Databáze: | OpenAIRE |
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