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Pilot Study Examining the Frequency of Several Gene Polymorphisms Involved in Morphine Pharmacodynamics and Pharmacokinetics in a Morbidly Obese Population

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Abstract

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.

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Abbreviations

ABCB1 :

ATP-binding cassette, subfamily B, member 1

BMI:

body mass index

COMT:

catechol-O-methyltransferase (enzyme and gene)

DNA:

deoxyribonucleic acid

EDTA:

ethylenediaminetetraacetic acid

M6G:

morphine-6-glucuronide

MAO-A:

monoamine oxydase A

MAO-B:

monoamine oxydase B

MOR:

mu opioid receptor

OPRM1 :

mu opioid receptor gene

P-gp:

P-glycoprotein

SNP:

single nucleotide polymorphism

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Authors and Affiliations

  1. Department of Nutrition and Endocrinology, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, 75013, France

    Célia Lloret Linares, Christine Poitou & Karine Clement

  2. Department of Internal Medicine, Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Unit of Therapeutic Research, 75475, Paris Cedex 10, France

    Célia Lloret Linares, Guy Simoneau, Jean François Bergmann & Stéphane Mouly

  3. Institut National de la Santé et de la Recherche Médicale U705, Centre National de la Recherche Scientifique UMR 7157, Faculty of Pharmacy, Paris-Cité Descartes University, Paris, 75006, France

    Aline Hajj, Jean Louis Laplanche, Jean-Pierre Lépine, Stéphane Mouly & Katell Peoc’h

  4. Department of Biochemistry and Molecular Biology, Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, 75475, Paris Cedex 10, France

    Aline Hajj, Jean Louis Laplanche & Katell Peoc’h

  5. Institut National de la Santé et de la Recherche Médicale, U872 team7, Nutriomique, Cordelier Research Center, Paris, 75006, France

    Christine Poitou & Karine Clement

  6. Hôpital Lariboisière, Service de Biochimie et Biologie Moléculaire, 2 rue Ambroise Paré, 75010, Paris, France

    Katell Peoc’h

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  1. Célia Lloret Linares
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  2. Aline Hajj
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Lloret Linares, C., Hajj, A., Poitou, C. et al. Pilot Study Examining the Frequency of Several Gene Polymorphisms Involved in Morphine Pharmacodynamics and Pharmacokinetics in a Morbidly Obese Population. OBES SURG 21, 1257–1264 (2011). https://doi.org/10.1007/s11695-010-0143-x

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