The effect of UGT1A9, CYP2B6 and CYP2C9 genes polymorphism on individual differences in propofol pharmacokinetics among Polish patients undergoing general anaesthesia.
Propofol (2,6-diisopropylphenol) is one of the safest and most commonly used anaesthetic agents for intravenous general anaesthesia. However, in clinical practice, a large inter-individual variability in response to propofol is observed. To limit the risk of adverse effects, pharmacogenetic investigations are recommended. The aim of our study was to verify the impact of genetic changes c.516G>T in the CYP2B6, c.98T>C in the UGT1A9 and c.1075A>C in the CYP2C9 genes on the individual propofol pharmacokinetic profile in the Polish patients undergoing general anaesthesia. Eighty-five patients from the Department of Anaesthesiology and Intensive Therapy, Regional Hospital in Poznan, Poland, anaesthetised with propofol for surgery, were enrolled in the study. We have genotyped CYP2B6, UGT1A9 and CYP2C9 polymorphisms with the use of pyrosequencing. HPLC measurements of propofol plasma concentration were applied for a pharmacokinetic analysis of the anaesthetic. We identified poor (20), intermediate (42) and rapid (23) metabolisers of propofol, which constituted 24%, 49% and 27% of the group, respectively. Homozygotes c.516 T/T in the CYP2B6 gene were statistically more often found in the rapid metabolisers group (p < 0.05). However, polymorphisms c.98T>C in the UGT1A9 and c.1075A>C in the CYP2C9 genes did not affect the pharmacokinetic profile of propofol. The mean propofol retention time (MRT) correlated with the patient's body mass index (BMI) (p < 0.05). From all the analysed changes, only polymorphism c.516G>T in the CYP2B6 gene and BMI affect the metabolism rate of propofol and may play an important role in the optimisation of propofol anaesthesia.
Department of Anaesthesiology and Intensive Therapy, Regional Hospital, Juraszow 7/19, 60-479, Poznan, Poland.
Adam
A
Mikstacki
Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479, Poznan, Poland.
Oliwia
O
Zakerska-Banaszak
Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479, Poznan, Poland.
Marzena
M
Skrzypczak-Zielinska
Department of Anaesthesiology and Intensive Therapy, Regional Hospital, Juraszow 7/19, 60-479, Poznan, Poland.
Barbara
B
Tamowicz
Laboratory of Neurobiology, Poznan University of Medical Sciences, Przybyszewskiego 49, 60-355, Poznan, Poland.
Michał
M
Prendecki
Laboratory of Neurobiology, Poznan University of Medical Sciences, Przybyszewskiego 49, 60-355, Poznan, Poland.
Jolanta
J
Dorszewska
Department of Computer Science and Statistics, Poznan University of Medical Sciences, Dabrowskiego 79, 60-529, Poznan, Poland.
Marta
M
Molinska-Glura
Department of Functional Anatomy, University School of Physical Education in Poznan, Krolowej Jadwigi 27/39, 61-871, Poznan, Poland.
Malgorzata
M
Waszak
Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479, Poznan, Poland. slomski@up.poznan.pl.|Department of Biochemistry and Biotechnology, University of Life Sciences, Dojazd 11, 60-632, Poznan, Poland. slomski@up.poznan.pl.
Ryszard
R
Slomski
D000328:Adult; D000768:Anesthesia, General; D018686:Anesthetics, Intravenous / Q000493:pharmacokinetics; D015992:Body Mass Index; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011044:Poland; D011110:Polymorphism, Genetic; D015742:Propofol / Q000493:pharmacokinetics*; D000090264:UDP-Glucuronosyltransferase 1A9
D018686:Anesthetics, Intravenous; C000715591:UGT1A9 protein, human; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D014453:Glucuronosyltransferase; D000090264:UDP-Glucuronosyltransferase 1A9; D015742:Propofol
General anaesthesia; Genotyping; Individual response; Pharmacokinetics; Propofol