Pilot study examining the frequency of several gene polymorphisms involved in morphine pharmacodynamics and pharmacokinetics in a morbidly obese population.
Morbidly obese patients are at significantly elevated risk of postsurgery complications and merit closer monitoring by health care professionals after bariatric surgery. It is now recognized that genetic factors influence individual patient's response to drug used in anesthesia and analgesia. Among the many drug administered by anesthetists, we focused in this pilot study on morphine, since morphine patient-controlled anesthesia in obese patients undergoing gastric bypass surgery is frequently prescribed. We examined the allelic frequency of three polymorphisms involved in morphine pharmacodynamics and pharmacokinetics in patients with body mass index (BMI) >40. One hundred and nine morbidly obese patients (BMI = 49.1 ± 7.7 kg/m²) were genotyped for three polymorphisms c.A118G of mu opioid receptor (OPRM1), c.C3435T of the P-glycoprotein gene (ABCB1), and p.Val158Met of catechol-O-methyltransferase gene (COMT). Allelic frequencies were 118G-0.22, C3435-0.55, and 158Met-0.5 in our whole population and 0.23, 0.5, and 0.47 in Caucasian population. Allelic frequencies did not differ according to gender. Mean BMI did no differ according to the allelic variant. OPRM1118G allele was more frequent in our population than in most previously described European populations. Since the concept of "personalized medicine" promises to individualize therapeutics and optimize medical treatment in term of efficacy and safety, especially when prescribing drugs with a narrow therapeutic index such as morphine, further clinical studies examining the clinical consequences of the OPRM1 c.A118G polymorphism in patients undergoing gastric bypass surgery are needed.
Lloret Linares
Célia
C
Department of Nutrition and Endocrinology, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France.
Hajj
Aline
A
Poitou
Christine
C
Simoneau
Guy
G
Clement
Karine
K
Laplanche
Jean Louis
JL
Lépine
Jean-Pierre
JP
Bergmann
Jean François
JF
Mouly
Stéphane
S
Peoc'h
Katell
K
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000701:Analgesics, Opioid / Q000493:pharmacokinetics*; D015992:Body Mass Index; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000493:pharmacokinetics*; D009767:Obesity, Morbid / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D010297:Paris; D010597:Pharmacogenetics; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D017450:Receptors, Opioid, mu / Q000235:genetics*; D017422:Sequence Analysis, DNA
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000701:Analgesics, Opioid; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D009020:Morphine; D002394:Catechol O-Methyltransferase
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