PMID- 24458221
OWN - NLM
STAT- MEDLINE
DCOM- 20140902
LR  - 20141028
IS  - 1421-9662 (Electronic)
IS  - 0001-5792 (Linking)
VI  - 132
IP  - 1
DP  - 2014
TI  - UGT1A1*28 polymorphism in chronic lymphocytic leukemia: the first investigation 
      of the polymorphism in disease susceptibility and its specific cytogenetic 
      abnormalities.
PG  - 59-67
LID - 10.1159/000355714 [doi]
AB  - 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.
CI  - (c) 2014 S. Karger AG, Basel.
FAU - Karakosta, Maria
AU  - Karakosta M
AD  - Laboratory of Cytogenetics, National Center for Scientific Research (NCSR) 
      'Demokritos', Athens, Greece.
FAU - Kalotychou, Vassiliki
AU  - Kalotychou V
FAU - Kostakis, Alkiviadis
AU  - Kostakis A
FAU - Pantelias, Gabriel
AU  - Pantelias G
FAU - Rombos, Ioannis
AU  - Rombos I
FAU - Kouraklis, Gregory
AU  - Kouraklis G
FAU - Manola, Kalliopi N
AU  - Manola KN
LA  - eng
PT  - Journal Article
DEP - 20140123
PL  - Switzerland
TA  - Acta Haematol
JT  - Acta haematologica
JID - 0141053
RN  - EC 2.4.1.- (UGT1A1 enzyme)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Case-Control Studies
MH  - Dinucleotide Repeats
MH  - Female
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease
MH  - Glucuronosyltransferase/deficiency/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*enzymology/*genetics
MH  - Male
MH  - Middle Aged
MH  - *Polymorphism, Genetic
MH  - Prognosis
EDAT- 2014/01/25 06:00
MHDA- 2014/09/03 06:00
CRDT- 2014/01/25 06:00
PHST- 2013/05/29 00:00 [received]
PHST- 2013/09/17 00:00 [accepted]
PHST- 2014/01/25 06:00 [entrez]
PHST- 2014/01/25 06:00 [pubmed]
PHST- 2014/09/03 06:00 [medline]
AID - 000355714 [pii]
AID - 10.1159/000355714 [doi]
PST - ppublish
SO  - Acta Haematol. 2014;132(1):59-67. doi: 10.1159/000355714. Epub 2014 Jan 23.