TY - JOUR
T1 - Variability in UDP-glucuronosyltransferase genes and morphine metabolism
T2 - Observations from a cross-sectional multicenter study in advanced cancer patients with pain
AU - Fladvad, Torill
AU - Klepstad, Pål
AU - Langaas, Mette
AU - Dale, Ola
AU - Kaasa, Stein
AU - Caraceni, Augusto
AU - Skorpen, Frank
PY - 2013/3
Y1 - 2013/3
N2 - OBJECTIVE: The objective of the present study was to determine whether genetic variability in UDP-glucuronosyltransferase (UGT) genes, together with clinical factors, contribute to variability in morphine glucuronide (M6G and M3G) to morphine serum concentration ratios in patients with advanced cancer receiving chronic morphine therapy. MATERIALS AND METHODS: A total of 41 polymorphisms and predicted haplotypes in the UGT2B7, UGT1A1, and UGT1A8 genes were analyzed in 759 patients who were recruited from the European Pharmacogenetic Opioid Study and received chronic morphine therapy by the oral route (n=635) or parenterally (n=124). The administration groups were analyzed separately by multiple linear regression analyses. RESULTS: Two haplotypes in UGT1A1/UGT1A8 were weak predictors of reduced M6G/morphine and M3G/morphine serum ratios after oral administration (false discovery rate-corrected P-values
AB - OBJECTIVE: The objective of the present study was to determine whether genetic variability in UDP-glucuronosyltransferase (UGT) genes, together with clinical factors, contribute to variability in morphine glucuronide (M6G and M3G) to morphine serum concentration ratios in patients with advanced cancer receiving chronic morphine therapy. MATERIALS AND METHODS: A total of 41 polymorphisms and predicted haplotypes in the UGT2B7, UGT1A1, and UGT1A8 genes were analyzed in 759 patients who were recruited from the European Pharmacogenetic Opioid Study and received chronic morphine therapy by the oral route (n=635) or parenterally (n=124). The administration groups were analyzed separately by multiple linear regression analyses. RESULTS: Two haplotypes in UGT1A1/UGT1A8 were weak predictors of reduced M6G/morphine and M3G/morphine serum ratios after oral administration (false discovery rate-corrected P-values
KW - morphine
KW - morphine-3-glucuronide
KW - morphine-6-glucuronide
KW - polymorphism
KW - UDP-glucuronosyltransferase
UR - http://www.scopus.com/inward/record.url?scp=84873412753&partnerID=8YFLogxK
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U2 - 10.1097/FPC.0b013e32835ce485
DO - 10.1097/FPC.0b013e32835ce485
M3 - Article
C2 - 23277092
AN - SCOPUS:84873412753
VL - 23
SP - 117
EP - 126
JO - Pharmacogenetics and Genomics
JF - Pharmacogenetics and Genomics
SN - 1744-6872
IS - 3
ER -