Skip to main content

2016 | OriginalPaper | Buchkapitel

7. Genetik

verfasst von : Prof. Dr. Dr. I. Cascorbi

Erschienen in: Rückenschmerzen und Nackenschmerzen

Verlag: Springer Berlin Heidelberg

Zusammenfassung

Die Kenntnisse über die genetische Variabilität und daraus folgende molekularbiologische Prozesse der Nozizeption erlauben ein zunehmend besseres Verständnis sowohl der Entstehung des Schmerzes als auch der analgetischen Therapie. So tragen genetische Faktoren zum Risiko der Bandscheibendegeneration mit bis zu 35 % bei, sind jedoch nur zu einem kleinen Teil auch mit Rückenschmerzen assoziiert. Zu Rückenschmerzen liegen für Varianten der GTP-Cyclohydrolase 1 die stärksten belastbaren Daten vor. Für die analgetische Wirkung von Opioiden und NSAIDs dagegen bestehen eindeutige Assoziationen zu genetischen Varianten jedoch nur in wenigen Fällen. Ein Beispiel ist der polymorphe Metabolismus von Codein. Für die personalisierte Therapie des Schmerzes bedarf es vielmehr eines systempharmakologischen Ansatzes, der genomweite Daten, Medikation und die Charakterisierung des individuellen Phänotyps einschließt.
Literatur
1.
Zurück zum Zitat Cox JJ, Reimann F, Nicholas AK, Thornton G, Roberts E, Springell K, Karbani G, Jafri H, Mannan J, Raashid Y, Al Gazali L, Hamamy H, Valente EM, Gorman S, Williams R, McHale DP, Wood JN, Gribble FM, Woods CG (2006) An SCN9A channelopathy causes congenital inability to experience pain. Nature 444:894–898CrossRefPubMed Cox JJ, Reimann F, Nicholas AK, Thornton G, Roberts E, Springell K, Karbani G, Jafri H, Mannan J, Raashid Y, Al Gazali L, Hamamy H, Valente EM, Gorman S, Williams R, McHale DP, Wood JN, Gribble FM, Woods CG (2006) An SCN9A channelopathy causes congenital inability to experience pain. Nature 444:894–898CrossRefPubMed
2.
Zurück zum Zitat Estany-Gestal A, Salgado-Barreira A, Sanchez-Diz P, Figueiras A (2011) Influence of CYP2C9 genetic variants on gastrointestinal bleeding associated with nonsteroidal anti-inflammatory drugs: a systematic critical review. Pharmacogenet Genomics 21:357–364CrossRefPubMed Estany-Gestal A, Salgado-Barreira A, Sanchez-Diz P, Figueiras A (2011) Influence of CYP2C9 genetic variants on gastrointestinal bleeding associated with nonsteroidal anti-inflammatory drugs: a systematic critical review. Pharmacogenet Genomics 21:357–364CrossRefPubMed
3.
Zurück zum Zitat Hartvigsen J, Nielsen J, Kyvik KO, Fejer R, Vach W, Iachine I, Leboeuf-Yde C (2009) Heritability of spinal pain and consequences of spinal pain: a comprehensive genetic epidemiologic analysis using a population-based sample of 15,328 twins ages 20–71 years. Arthritis Rheum 61:1343–1351CrossRefPubMed Hartvigsen J, Nielsen J, Kyvik KO, Fejer R, Vach W, Iachine I, Leboeuf-Yde C (2009) Heritability of spinal pain and consequences of spinal pain: a comprehensive genetic epidemiologic analysis using a population-based sample of 15,328 twins ages 20–71 years. Arthritis Rheum 61:1343–1351CrossRefPubMed
4.
5.
Zurück zum Zitat Kirchheiner J, Keulen JT, Bauer S, Roots I, Brockmoller J (2008) Effects of the CYP2D6 gene duplication on the pharmacokinetics and pharmacodynamics of tramadol. J Clin Psychopharmacol 28:78–83CrossRefPubMed Kirchheiner J, Keulen JT, Bauer S, Roots I, Brockmoller J (2008) Effects of the CYP2D6 gene duplication on the pharmacokinetics and pharmacodynamics of tramadol. J Clin Psychopharmacol 28:78–83CrossRefPubMed
6.
Zurück zum Zitat Livshits G, Popham M, Malkin I, Sambrook PN, Macgregor AJ, Spector T, Williams FM (2011) Lumbar disc degeneration and genetic factors are the main risk factors for low back pain in women: the UK Twin Spine Study. Ann Rheum Dis 70: 1740–1745CrossRefPubMedPubMedCentral Livshits G, Popham M, Malkin I, Sambrook PN, Macgregor AJ, Spector T, Williams FM (2011) Lumbar disc degeneration and genetic factors are the main risk factors for low back pain in women: the UK Twin Spine Study. Ann Rheum Dis 70: 1740–1745CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Lotsch J, Geisslinger G, Tegeder I (2009a) Genetic modulation of the pharmacological treatment of pain. Pharmacol Ther 124: 168–184 Lotsch J, Geisslinger G, Tegeder I (2009a) Genetic modulation of the pharmacological treatment of pain. Pharmacol Ther 124: 168–184
8.
Zurück zum Zitat Lotsch J, von Hentig N, Freynhagen R, Griessinger N, Zimmermann M, Doehring A, Rohrbacher M, Sittl R, Geisslinger G (2009b) Cross-sectional analysis of the influence of currently known pharmacogenetic modulators on opioid therapy in outpatient pain centers. Pharmacogenet Genomics 19:429–436 Lotsch J, von Hentig N, Freynhagen R, Griessinger N, Zimmermann M, Doehring A, Rohrbacher M, Sittl R, Geisslinger G (2009b) Cross-sectional analysis of the influence of currently known pharmacogenetic modulators on opioid therapy in outpatient pain centers. Pharmacogenet Genomics 19:429–436
9.
Zurück zum Zitat Mio F, Chiba K, Hirose Y, Kawaguchi Y, Mikami Y, Oya T, Mori M, Kamata M, Matsumoto M, Ozaki K, Tanaka T, Takahashi A, Kubo T, Kimura T, Toyama Y, Ikegawa S (2007) A functional polymorphism in COL11A1, which encodes the alpha 1 chain of type XI collagen, is associated with susceptibility to lumbar disc herniation. Am J Hum Genet 81:1271–1277CrossRefPubMedPubMedCentral Mio F, Chiba K, Hirose Y, Kawaguchi Y, Mikami Y, Oya T, Mori M, Kamata M, Matsumoto M, Ozaki K, Tanaka T, Takahashi A, Kubo T, Kimura T, Toyama Y, Ikegawa S (2007) A functional polymorphism in COL11A1, which encodes the alpha 1 chain of type XI collagen, is associated with susceptibility to lumbar disc herniation. Am J Hum Genet 81:1271–1277CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Oertel BG, Kettner M, Scholich K, Renne C, Roskam B, Geisslinger G, Schmidt PH, Lotsch J (2009) A common human micro-opioid receptor genetic variant diminishes the receptor signaling efficacy in brain regions processing the sensory information of pain. J Biol Chem 284:6530–6535CrossRefPubMed Oertel BG, Kettner M, Scholich K, Renne C, Roskam B, Geisslinger G, Schmidt PH, Lotsch J (2009) A common human micro-opioid receptor genetic variant diminishes the receptor signaling efficacy in brain regions processing the sensory information of pain. J Biol Chem 284:6530–6535CrossRefPubMed
11.
Zurück zum Zitat Paassilta P, Lohiniva J, Goring HH, Perala M, Raina SS, Karppinen J, Hakala M, Palm T, Kroger H, Kaitila I, Vanharanta H, Ott J, Ala-Kokko L (2001) Identification of a novel common genetic risk factor for lumbar disk disease. JAMA 285:1843–1849CrossRefPubMed Paassilta P, Lohiniva J, Goring HH, Perala M, Raina SS, Karppinen J, Hakala M, Palm T, Kroger H, Kaitila I, Vanharanta H, Ott J, Ala-Kokko L (2001) Identification of a novel common genetic risk factor for lumbar disk disease. JAMA 285:1843–1849CrossRefPubMed
12.
Zurück zum Zitat Seki S, Kawaguchi Y, Chiba K, Mikami Y, Kizawa H, Oya T, Mio F, Mori M, Miyamoto Y, Masuda I, Tsunoda T, Kamata M, Kubo T, Toyama Y, Kimura T, Nakamura Y, Ikegawa S (2005) A functional SNP in CILP, encoding cartilage intermediate layer protein, is associated with susceptibility to lumbar disc disease. Nat Genet 37:607–612CrossRefPubMed Seki S, Kawaguchi Y, Chiba K, Mikami Y, Kizawa H, Oya T, Mio F, Mori M, Miyamoto Y, Masuda I, Tsunoda T, Kamata M, Kubo T, Toyama Y, Kimura T, Nakamura Y, Ikegawa S (2005) A functional SNP in CILP, encoding cartilage intermediate layer protein, is associated with susceptibility to lumbar disc disease. Nat Genet 37:607–612CrossRefPubMed
13.
Zurück zum Zitat Solovieva S, Leino-Arjas P, Saarela J, Luoma K, Raininko R, Riihimaki H (2004) Possible association of interleukin 1 gene locus polymorphisms with low back pain. Pain 109:8–19CrossRefPubMed Solovieva S, Leino-Arjas P, Saarela J, Luoma K, Raininko R, Riihimaki H (2004) Possible association of interleukin 1 gene locus polymorphisms with low back pain. Pain 109:8–19CrossRefPubMed
14.
Zurück zum Zitat Solovieva S, Noponen N, Mannikko M, Leino-Arjas P, Luoma K, Raininko R, Ala-Kokko L, Riihimaki H (2007) Association between the aggrecan gene variable number of tandem repeats polymorphism and intervertebral disc degeneration. Spine (Phila Pa 1976) 32:1700–1705CrossRefPubMed Solovieva S, Noponen N, Mannikko M, Leino-Arjas P, Luoma K, Raininko R, Ala-Kokko L, Riihimaki H (2007) Association between the aggrecan gene variable number of tandem repeats polymorphism and intervertebral disc degeneration. Spine (Phila Pa 1976) 32:1700–1705CrossRefPubMed
15.
Zurück zum Zitat Somogyi AA, Barratt DT, Coller JK (2007) Pharmacogenetics of opioids. Clin Pharmacol Ther 81:429–444CrossRefPubMed Somogyi AA, Barratt DT, Coller JK (2007) Pharmacogenetics of opioids. Clin Pharmacol Ther 81:429–444CrossRefPubMed
16.
Zurück zum Zitat Stamer UM, Stuber F (2008) Codeine induced respiratory depression in a child. Paediatr Anaesth 18:272–273CrossRefPubMed Stamer UM, Stuber F (2008) Codeine induced respiratory depression in a child. Paediatr Anaesth 18:272–273CrossRefPubMed
17.
Zurück zum Zitat Tegeder I, Lötsch J (2009) Current evidence for a modulation of low back pain by human genetic variants. J Cell Mol Med 13:1605–1619CrossRefPubMed Tegeder I, Lötsch J (2009) Current evidence for a modulation of low back pain by human genetic variants. J Cell Mol Med 13:1605–1619CrossRefPubMed
18.
Zurück zum Zitat Tegeder I, Costigan M, Griffin RS, Abele A, Belfer I, Schmidt H, Ehnert C, Nejim J, Marian C, Scholz J, Wu T, Allchorne A, Diatchenko L, Binshtok AM, Goldman D, Adolph J, Sama S, Atlas SJ, Carlezon WA, Parsegian A, Lotsch J, Fillingim RB, Maixner W, Geisslinger G, Max MB, Woolf CJ (2006) GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence. Nat Med 12:1269–1277CrossRefPubMed Tegeder I, Costigan M, Griffin RS, Abele A, Belfer I, Schmidt H, Ehnert C, Nejim J, Marian C, Scholz J, Wu T, Allchorne A, Diatchenko L, Binshtok AM, Goldman D, Adolph J, Sama S, Atlas SJ, Carlezon WA, Parsegian A, Lotsch J, Fillingim RB, Maixner W, Geisslinger G, Max MB, Woolf CJ (2006) GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence. Nat Med 12:1269–1277CrossRefPubMed
19.
Zurück zum Zitat Tilkeridis C, Bei T, Garantziotis S, Stratakis CA (2005) Association of a COL1A1 polymorphism with lumbar disc disease in young military recruits. J Med Genet 42:e44CrossRefPubMedPubMedCentral Tilkeridis C, Bei T, Garantziotis S, Stratakis CA (2005) Association of a COL1A1 polymorphism with lumbar disc disease in young military recruits. J Med Genet 42:e44CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Yuan HY, Tang Y, Liang YX, Lei L, Xiao GB, Wang S, Xia ZL (2010) Matrix metalloproteinase-3 and vitamin d receptor genetic polymorphisms, and their interactions with occupational exposure in lumbar disc degeneration. J Occup Health 52:23–30CrossRefPubMed Yuan HY, Tang Y, Liang YX, Lei L, Xiao GB, Wang S, Xia ZL (2010) Matrix metalloproteinase-3 and vitamin d receptor genetic polymorphisms, and their interactions with occupational exposure in lumbar disc degeneration. J Occup Health 52:23–30CrossRefPubMed
21.
Zurück zum Zitat Zhang Y, Wang D, Johnson AD, Papp AC, Sadee W (2005) Allelic expression imbalance of human mu opioid receptor (OPRM1) caused by variant A118G. J Biol Chem 280:32618–32624CrossRefPubMed Zhang Y, Wang D, Johnson AD, Papp AC, Sadee W (2005) Allelic expression imbalance of human mu opioid receptor (OPRM1) caused by variant A118G. J Biol Chem 280:32618–32624CrossRefPubMed
22.
Zurück zum Zitat Hirose Y, Chiba K, Karasugi T, Nakajima M, Kawaguchi Y, Mikami Y, Furuichi T, Mio F, Miyake A, Miyamoto T, Ozaki K, Takahashi A, Mizuta H, Kubo T, Kimura T, Tanaka T, Toyama Y, lkegawa S (2008) A functional polymorphism in THBS2 that affects alternative splicing and MMP binding is associated with lumbar-disc herniation. Am J Hum Genet 82:1122–1129CrossRefPubMedPubMedCentral Hirose Y, Chiba K, Karasugi T, Nakajima M, Kawaguchi Y, Mikami Y, Furuichi T, Mio F, Miyake A, Miyamoto T, Ozaki K, Takahashi A, Mizuta H, Kubo T, Kimura T, Tanaka T, Toyama Y, lkegawa S (2008) A functional polymorphism in THBS2 that affects alternative splicing and MMP binding is associated with lumbar-disc herniation. Am J Hum Genet 82:1122–1129CrossRefPubMedPubMedCentral
Metadaten
Titel
Genetik
verfasst von
Prof. Dr. Dr. I. Cascorbi
Copyright-Jahr
2016
Verlag
Springer Berlin Heidelberg
DOI
https://doi.org/10.1007/978-3-642-29775-5_7

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.