Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
CNS Drugs
Published in: CNS Drugs 2/2007

01-02-2007 | Review Article

Various Pharmacogenetic Aspects of Antiepileptic Drug Therapy

A Review

Authors: Dr Michael W. Mann, Gerard Pons

Published in: CNS Drugs | Issue 2/2007

Login to get access

Abstract

Pharmacogenetics concerns the influence of an individual’s genetic background on the pharmacokinetics and pharmacodynamics of xenobiotics.
Much of the pharmacogenetic data in the field of epilepsy deals with the pharmacokinetics of antiepileptic drugs (AEDs). In particular, two polymorphisms of cytochrome P450 2C9 are known to slow down the metabolism of phenytoin to a degree that increases the risk of the neurotoxic adverse effects of this drug among carriers of these polymorphisms. A significant number of patients with epilepsy do not respond to AEDs and such pharmacoresistance is a major, largely unsolved, problem that is likely to be multifactorial in nature. In this regard, genetic factors may influence transmembrane drug transporter proteins, thereby modifying the intracerebral penetration of AEDs.
Monogenic idiopathic epilepsies are rare and frequently associated with ion channel mutations; however, to date, a consistent relationship between changes in channel properties and clinical phenotype has not been established nor has any association between genotype and response to specific treatment options. Polymorphisms of drug targets may represent another genetic facet in epilepsy: a recent study demonstrated for the first time a polymorphism of a drug target (the α-subunit of a voltage-gated sodium channel) associated in clinical practice with differing response to two classic AEDs.
Adverse drug reactions and teratogenicity of AEDs remain a major concern. Whole-genome single nucleotide polymorphism profiling might in the future help to determine genetic predisposing factors for adverse drug reactions. Recently, in Han Chinese treated with carbamazepine and presenting with Stevens-Johnson syndrome, a strong association was found with HLA B*1502.
If genetically targeted drug development becomes more affordable/cost efficient in the near future, the development of new drugs for relatively rare diseases could become economically viable for the pharmaceutical industry. The synergy of lower trial costs and efficacy-based prescribing may reduce the cost of medical treatment for a particular disease. This hypothetical advantage of the practical use of pharmacogenetics is, however, counterbalanced by several possible dangers, including illicit data mining and the development of a human ‘genetic underclass’ with the risk of exclusion from, for example employment or health insurance, because of an ‘unfavourable’ genetic profile.
Footnotes
1
Each number preceded by a * denotes a particular polymorphism. The increasing numbers indicate the chronological order of the description of the polymorphism. *1 or ‘1’ denotes the wild type without a mutation. *1/*1 indicates the absence of a mutation in both alleles. The mutated base can be indicated in parentheses (A = adenine, C = cytosine, G = guanine, T = thymine). In CYP2C9 this is illustrated by the replacement of A by C: A→C for *3/*3 (C/C) and *3/*1 (C/ A).
 
Literature
1.
2.
Meyer UA. Pharmacogenetics: five decades of therapeutic lessons from genetic diversity. Nat Rev 2004 Sep; 5: 669–76
3.
Dahl ML. Cytochrome P450 phenotyping/genotyping in patients receiving antipsychotics: useful aid to prescribing? Clin Pharmacokinetic 2002; 41: 453–70CrossRef
4.
Fukuda K, Ohta T, Oshima Y, et al. Specific CYP3A4 inhibitors in grapefruit juice: furocoumarin dimers as components of drug interaction. Pharmacogenetics 1997 Oct; 7: 191–396CrossRef
5.
Snyder LH. Studies in human inheritance IX: the inheritance of taste deficiency in man. Ohio J Sci 1932; 32: 436–68
6.
Wilkinson GR. Drug metabolism and variability among patients in drug response. N Engl J Med 2005 May 26; 352: 2211–21PubMedCrossRef
7.
Kim RB, Leake BF, Choo EF, et al. Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clin Pharmacol Ther 2001; 70: 189–99PubMedCrossRef
8.
Sachse C, Brockmoller J, Bauer S, et al. Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences. Am J Hum Genet 1997; 60: 284–95PubMed
9.
Floyd M, Gervasini G, Masica A, et al. Genotype-phenotype associations for common CYP3A4 and CYP3A5 variants in the basal and induced metabolism of midazolam in European-and African-American men and women. Pharmacogenetics 2003; 13: 595–606PubMedCrossRef
10.
Lee CR, Goldstein JA, Pieper JA. Cytochrome P450 2C9 polymorphisms: a comprehensive review of the in-vitro and human data. Pharmacogenetics 2002; 12: 251–63PubMedCrossRef
11.
Bertilsson L, Lou YQ, Du YL, et al. Pronounced differences between native Chinese and Swedish populations in the olymorphic hydroxylations of debrisoquin and S-mephenytoin. Clin Pharmacol Ther 1992; 51: 388–97PubMedCrossRef
12.
Bertilsson L. Geographical/interracial differences in polymorphic drug oxidation: current state of knowledge of cytochromes P450(CYP)2D6 and 2C19. Clin Pharmacokinet 1995; 29(3): 192–209PubMedCrossRef
13.
Lonjou C, Thomas L, Borot N, et al. A marker for Stevens-Johnson syndrome …: ethnicity matters. Pharmacogenomics J 2006; (6): 265-8
14.
Kerb R. Implications of genetic polymorphisms in drug transporters for pharmacotherapy. Cancer Lett 2006; 234(1): 4–33PubMedCrossRef
15.
Garrod AE. The incidence of alkaptonuria: a study in chemical individuality. Lancet 1902 Dec; 160: 1616–20CrossRef
16.
Garrod AE. The Croonian lectures on inborn errors of metabolism: lecture II. Alkaptonuria. Lancet 1908; II: 73–9
17.
Garrod AE. The inborn errors of metabolism. London: Oxford University Press, 1909
18.
Vogel F. Moderne Probleme der Humangenetik. Ergebn Inn Med Kinderheilkunde 1959; 12: 52–125CrossRef
19.
20.
21.
Lehmann H, Ryan E. The familial incidence of low pseudocholinesterase level [letter]. Lancet 1956; 271: 124PubMedCrossRef
22.
Kalow W, Staron N. On distribution and inheritance of atypical forms of human serum cholinesterase, as indicated by dibucaine numbers. Can J Med Sci 1957; 35: 1305–20
23.
Kalow W, Gunn DR. Some statistical data on atypical cholinesterase of human serum. Ann Hum Genet 1959; 23: 239–50PubMedCrossRef
24.
Price Evans DA, Manley KA, McKusick VA. Genetic control of isoniazid metabolism in man. BMJ 1960; 2: 485–90CrossRef
25.
Solinas C, Vaida FJ. Epilepsy and porphyria: new perspectives. J Clin Nerosci 2004; 11(4): 356–61CrossRef
26.
Zadra M, Grandi R, Erli LC, et al. Treatment of seizures in acute intermittent porphyria: safety and efficacy of gabapentin. Seizure 1998; 5: 415–6CrossRef
27.
Friedemann P, Meencke H-J. Levetiracetam in focal epilepsy and hepatic porphyria: a case report. Epilepsia 2004; 45(5): 559–60CrossRef
28.
29.
30.
Depondt C. The potential of pharmacogenetics in the treatment of epilepsy. Eur J Paediatr Neurol 2006; 10: 57–65PubMedCrossRef
31.
Handschin C, Meyer UA. Induction of drug metabolism: the role of nuclear receptors. Pharmacol Rev 2003; 55: 649–73PubMedCrossRef
32.
Anderson GD. Pharmacogenetics and enzyme induction/inhibition properties of antiepileptic drugs. Neurology 2004 Nov; 63Suppl. 4: S3–8PubMedCrossRef
33.
Amirimani B, Ning B, Deitz AC, et al. Increased transcriptional activity of the CYP3A4*1B promoter variant. Environ Mol Mutagen 2003; 42(4): 299–305PubMedCrossRef
34.
Wojnowski L, Kamdem LK. Clinical implications of CYP3A polymorphisms. Expert Opin Drug Metab Toxicol 2006; 2(2): 171–82PubMedCrossRef
35.
Ariyoshi N, Miyazaki M, Toide K, et al. A single nucleotide polymorphism of CYP 2B6 found in Japanese enhances catalytic activity by auto activation. Biochem Biophys Res Commun. 2001; 281(5): 1256–60PubMedCrossRef
36.
Xie HJ, Yasar U, Lundgren S, et al. Role of polymorphic human CYP2B6 in cyclophosphamid bioactivation. Pharmacogenom J 2003; 3: 53–61CrossRef
37.
Xie HJ, Griskevicius L, Stahle L, et al. Pharmacogenetics of cyclophosphamide in patients with hematological malignancies. Eur J Pharm Sci 2006; 27: 54–61PubMedCrossRef
38.
Xiao ZS, Goldenstein JA, Xie HG, et al. Differences in the incidence of the CYP2C19 polymorphism affecting the S-mephenytoin phenotype in Chinese Han and Bai populations and identification of a new rare CYP2C19 mutant allele. J Pharmacol Exp Ther 1997; 281: 604–9PubMed
39.
Xie H-G, Wood AJJ, Kim RB, et al. Genetic variability in CYP3A5 and its possible consequences. Pharmacogenomics 2004; 5(3): 243–72PubMedCrossRef
40.
Lamba JK, Lin YS, Schuetz EG, et al. Genetic contribution to variable human CYP3A4-mediated metabolism. Adv Drug Deliv Rev 2002; 54(10): 1271–94PubMedCrossRef
41.
Lamba JK, Lin YS, Thummel KG, et al. Common allelic variants of cytochrome P450 3A4 and their prevalence in different populations. Pharmacogenetics. 2002; 12(2): 121–32PubMedCrossRef
42.
Rettie AE, Wienkers LC, Gonzalez FJ, et al. Impaired S-warfain metabolism catalysed by the R144C allelic variant of CYP2C9. Pharmacogenetics 1994; 4: 39–42PubMedCrossRef
43.
Haining RL, Hunter AP, Veronese ME, et al. Allelic variants of human cytochrome P450 2C9: baculovirus-mediated expression, urification, structural characterization, substrate stereoselectivity, and prochiral selectivity of the wild-type and I359L mutant forms. Arch Biochem Biophys 1996; 333: 447–58PubMedCrossRef
44.
Takahashi H, Echizen H. Pharmacogenetics of warfarin elimination and its clinical implications. Clin Pharmacokinet 2001; 40: 587–603PubMedCrossRef
45.
Hillman MA, Wilke RA, Caldwell MF, et al. Relative impact of covariates in prescribing warfarin according to CYP2C9 genotype. Pharmacogenetics 2004 Aug; 14(8): 539–47PubMedCrossRef
46.
Brandolese R, Scordo MG, Spina E, et al. Severe phenytoin intoxication in a subject homozygous for CYP2C9*3. Clin Pharmacol Ther 2001 Oct; 70: 391–4PubMed
47.
Kidd RS, Curry TB, Gallagher S, et al. Identification of a null allele of CYP2C9 in an African-American exhibiting toxic phenytoin. Pharmacogenetics 2001 Dec; 11: 803–8PubMedCrossRef
48.
Mamiya K, Ieiri I, Shimamoto J, et al. The effects of genetic polymorphisms of CYP2C9 and CY2C19 on phenytoin metabolism in Japanese adult patients with epilepsy: studies in stereoselective hydroxylation and population pharmacokinetics. Epilepsia 1998; 39: 1317–23PubMedCrossRef
49.
Soga Y, Nishimura F, Ohtsuka Y, et al. CYP2C polymorphisms, phenytoin metabolism and gingival overgrowth in epileptic subjects. Life Sci 2004; 74: 827–34PubMedCrossRef
50.
Schwarz UI. Clinical relevance of genetic polymorphisms in the human CYP2C9 gene. Eur J Clin Invest 2003; 33Suppl. 2: 23–30PubMedCrossRef
51.
Van der Weide J, Steijns LSW, van Weelden JM, et al. The effect of genetic polymorphism of cytochrome P450 CYP2C9 on phenytoin dose requirement. Pharmacogenetics 2001; 11: 287–91PubMedCrossRef
52.
Tate SK, Depondt C, Sisodiya SM, et al. Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin. Proc Natl Acad Sci USA 2005 Apr; 102(15): 5507–12PubMedCrossRef
53.
Odani A, Hashimoto Y, Otsuki Y, et al. Genetic polymorphism of the CYP2C subfamily and its effect on the pharmacokinetics of phenytoin in Japanese patients with epilepsy. Clin Pharmacol Ther 1997; 62: 287–92PubMedCrossRef
54.
Kwan P, Brodie MJ. Phenobarbital for the treatment of epilepsy in the 21st century: a critical review. Epilepsia 2004; 45: 1141–9PubMedCrossRef
55.
Mamiya K, Hadama A, Yukawa E, et al. CYP2C19 polymorphism effect on phenobarbitone. Pharmacokinetics in Japanese patients with epilepsy: analysis by population pharmacokinetics. Eur J Clin Pharmacol 2000 Feb–Mar; 55(11–12): 821–5PubMedCrossRef
56.
Hadama A, Ieri I, Morita T, et al. P-hydroxylation of phenobarbital: relationship to (S)-mephenytoin hydroxylation (CYP2C19) polymorphism. Ther Drug Monit 2001; 23: 115–8PubMedCrossRef
57.
Ferraro TN, Buono RJ. The relationship between the pharmacology of antiepileptic drugs and human gene variation: an overview. Epilepsy Behav 2005; 7: 18–36PubMedCrossRef
58.
Green VJ, Pirmohamed M, Kitteringham NR, et al. Genetic analysis of microsomal epoxide hydrolase in patients with carbamazepine hypersensitivity. Biochem Pharmacol 1995; 50(9): 1353–9PubMedCrossRef
59.
Ketter TA, Frye MA, Cora-Locatelli G, et al. Metabolism and excretion of mood stabilizers and new anticonvulsants. Cell Mol Neurobiol 1999; 19: 511–32PubMedCrossRef
60.
Sadeque AJM, Fisher MB, Korzekwa KR, et al. Human CYP2C9 and CYP2A6 mediate formation of the hepatotoxin 4-ene-valproic acid. J Pharmacol Exp Ther 1997; 283(2): 698–703PubMed
61.
Ho PC, Abbott FS, Zanger UM, et al. Influence of CYP2C9 genotypes on the formation of a hepatotoxic metabolite of valproic acid in human liver microsomes. Pharmacogenomics J 2003; 3(6): 335–42PubMedCrossRef
62.
Rogiers V, Akrawi M, Vercruysse A, et al. Effects of the anticonvulsant, valproate, on the expression of components of the cytochrome P-450-mediated monooxygenase system and glutathione S-transferases. Eur J Biochem 1995; 231(2): 337–43PubMedCrossRef
63.
Krishnaswamy S, Hao Q, Al-Rohaimi A, et al. UDP Glucuronosyltransferase (UGT) 1A6 pharmacogenetics: II. Functional impact of the three most common nonsynonymous UGT1A6 polymorphisms (S7A, T181A, and R184S) J Pharmacol Exp Ther 2005; 313(3): 1340–6PubMed
64.
Ciotti M, Marrone A, Potter C, et al. Genetic polymorphism in the human UGT1A6 (planar phenol) UDP-glucuronyltransferase: pharmacological implications. Pharmacogenetics 1997; 7: 485–95PubMedCrossRef
65.
Nagar S, Zalatoria JJ, Blanchard RL. Human UGT1A6 pharmacogenetics: identification of a novel SNP, characterization of allele frequencies and functional analysis of recombinant allozymes in human liver tissue and in cultured cells. Pharmacogenetics 2004; 14: 487–99PubMedCrossRef
66.
Krishnaswamy S, Hao Q, Al-Rohaimi A, et al. UDP-glucuronosyltransferase (UGT)1A6 pharmacogenetics: I. Identification of polymorphisms in the 5′-regulatory and exon 1 regions, and association with human liver UGT1A6 gene expression and glucuronidation. J Pharmacol Exp Ther 2005; 313: 1331–9
67.
Kobayashi K, Morita J, Chiba K, et al. Pharmacogenetic roles of CYP2C19 and CYP2B6 in the metabolism of R-and S-mephobarbital in humans. Pharmacogenetics 2004; 14: 549–56PubMedCrossRef
68.
Liston HL, Markowitz JS, DeVane CL. Drug glucuronidation in clinical psychopharmacology. J Clin Psychopharmacol 2001 Oct; 21(5): 500–15PubMedCrossRef
69.
Rowland A, Elliot DJ, Williams JA, et al. In vitro characterization of lamotrigine N2-glucuronidation and the lamotriginevalproic acid interaction. Drug Metab Dispos 2006; 34(6): 1055–62PubMed
70.
Ehmer U, Vogel A, Schütte JK, et al. Variation of hepatic glucuronidation: novel functional polymorphisms of the UDP-glucuronosyltranferase UGT1A4. Hepatology 2004; 39: 970–7PubMedCrossRef
71.
72.
Scheffer GL, Wijngaard PLJ, Flens MJ, et al. The drug resistance-related protein LRP is the human major vault protein. Nature Medicine 1995; 1: 578–82PubMedCrossRef
73.
Löscher W, Potschka H. Role of multidrug transporter in pharmacoresistance to antiepileptic drugs. J Pharmacol Exp Ther 2002; 301(1): 7–14PubMedCrossRef
74.
Kwan P, Brodie MJ. Potential role of drug transporters in the pathogenesis of medically intractable epilepsy. Epilepsia 2005 Feb; 46(2): 224–35PubMedCrossRef
75.
76.
Sisodiya SM, Lin WR, Harding BN, et al. Drug resistance in epilepsy: expression of drug resistance proteins in common causes of refractory epilepsy. Brain 2002 Jan; 125: 22–31PubMedCrossRef
77.
Juliano RL, Ling V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 1976; 455(1): 152–62PubMedCrossRef
78.
Dean M, Rzhetsky A, Allikmets R. The human ATP-binding cassette (ABC) transporter superfamily. Genome Res 2001; 11: 1156–66PubMedCrossRef
79.
80.
Brinkmann U, Roots I, Eichelbaum M. Pharmacogenetics of the human drug-transporter gene MDR1: impact of polymorphisms on pharmacotherapy. Drug Discov Today 2001 Aug 15; 6: 835–9PubMedCrossRef
81.
Borst P, Evers R, Kool M, et al. A family of drug transporters: the multidrug resistance-associated proteins. J Natl Cancer Inst 2000; 92: 1295–302PubMedCrossRef
82.
Wijnholds J. Drug resistance caused by multidrug resistance-associated proteins: mechanisms of drug resistance in epilepsy: lessons from oncology. Chichester: John Wiley & Sons Ltd, 2002, 82
83.
Sills GJ, Kwan P, Butler E, et al. P-glycoprotein mediated efflux of antiepileptic drugs: preliminary studies in mdr1 knockout mice. Epilepsy Behav 2002; 3: 427–32PubMedCrossRef
84.
Owen A, Pirmohamed M, Tettey JN, et al. Carbamazepine is not a substrate for P-glycoprotein. Br J Clin Pharmacol 2001 Apr; 51(4): 345–9PubMedCrossRef
85.
Potschka H, Baltes S, Löscher W. Inhibition of multidrug transporters by verapamil or probenecid does not alter blood-brain barrier penetration of levetiracetam in rats. Epilepsy Res 2004; 58: 85–91PubMedCrossRef
86.
Lee G, Dallas S, Hong M, et al. Drug transporters in the central nervous system: brain barriers and brain parenchyma considerations. Pharmacol Rev 2001; 53(4): 569–96PubMed
87.
Johnstone RW, Ruefli AA, Tainton KM, et al. A role for P-glycoprotein in regulating cell death. Leukemia Lymphoma 2000 Jun; 38(1–2): 1–11PubMed
88.
Sisodiya SM, Lin WR, Squier MV, et al. Multidrug-resistance protein 1 in focal cortical dysplasia. Lancet 2001 Jan 6; 357: 42–3PubMedCrossRef
89.
Sakaeda T. MDR1 genotype-related pharmacokinetics: fact or fiction? Drug Metab Pharmacokinet 2005; 20(6): 391–414PubMedCrossRef
90.
Hoffmeyer S, Burk O, von Richter O, et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci USA 2000; 97(7): 3473–8PubMedCrossRef
91.
Siddiqui A, Kerb R, Weale ME, et al. Association of multidrug resistance in epilepsy with a polymorphism in the drug-transporter gene ABCB1. N Engl J Med 2003; 348: 1442–8PubMedCrossRef
92.
Zimprich F, Sunder-Plassmann R, Stogmann E, et al. Association of an ABCB1 gene haplotype with pharmacoresistance in temporal lobe epilepsy. Neurology 2004; 63: 1087–9PubMedCrossRef
93.
Hung CC, Tai JJ, Lin CJ, et al. Complex haplotypic effects of the ABCB1 gene on epilepsy treatment response. Pharmacogenomics 2005; 6(4): 411–7PubMedCrossRef
94.
Seo T, Ishitsu T, Ueda N, et al. ABCB1 polymorphisms influence the response to antiepileptic drugs in Japanese epilepsy patients. Pharmacogenomics 2006; 7(4): 551–61PubMedCrossRef
95.
Tan NCK, Heron SE, Scheffer IE, et al. Failure to confirm association of a polymorphism in ABCB1 with multidrug-resistant epilepsy. Neurology 2004; 63: 1090–2PubMedCrossRef
96.
Sills GJ, Mohanraj R, Butler E, et al. Lack of association between the C3435T polymorphism in the human multidrug resistance (MDR1) gene and response to antiepileptic drug treatment. Epilepsia 2005; 46(5): 643–7PubMedCrossRef
97.
Kim YO, Kim MK, Woo YJ, et al. Single nucleotide polymorphisms in the multidrug resistance 1 gene in Korean epileptics. Seizure 2006; 15: 67–72PubMedCrossRef
98.
Leschziner G, Jorgensen AI, Andrew T, et al. Clinical factors and ABCB1 polymorphisms in prediction of antiepileptic drug response: a prospective cohort study. Lancet Neuro 2006 Aug; 5: 668–76CrossRef
99.
100.
Cardon LR, Bell JI. Association study designs for complex diseases. Nat Rev Genet 2001; 2(2): 91–9PubMedCrossRef
101.
Scheffer IE, Berkovic SF. The genetics of human epilepsy. Trends in Pharmacol Sci 2003; 24(8): 428–33CrossRef
102.
Leppert M, Anderson VE, Quattlebaum T, et al. Benign familial neonatal convulsions linked to genetic markers on chromosome 20. Nature 1989; 337: 647–8PubMedCrossRef
103.
Gourfinkel-An I, Baulac S, Nabbout R, et al. Monogenic idiopathic epilepsies. Lancet Neurol 2004; 3: 209–18PubMedCrossRef
104.
Baulac S, Gourfinkel-An I, Nabbout R, et al. Fever, genes and epilepsy. Lancet Neurol 2004; 3: 421–30PubMedCrossRef
105.
106.
Ottmann R, Winawer MR, Kalachnikov S, et al. LGI1 mutations in autosomal dominant partial epilepsy with auditory features. Neurology 2004; 62: 1120–6CrossRef
107.
Escayg A, De Waard M, Lee DD, et al. Coding and noncoding variation of the human calcium-channel β4 subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. Am J Hum Genet 2000; 66: 1531–9PubMedCrossRef
108.
Jouvenceau A, Eunson LH, Spauschus A, et al. Human epilepsy associated with dysfunction of the brain P/Q-type calcium channel. Lancet 2001; 358(9284): 801–7PubMedCrossRef
109.
Brodtkorb E, Michler RP, Gu W, et al. Speech-induced aphasic seizures in epilepsy caused by LGI 1 mutation. Epilepsia 2005 Jun; 46: 963–6PubMedCrossRef
110.
Vadlamudi L, Scheffer IE, Berkovic SF. Genetics of temporal lobe epilepsy. J Neurol Neurosurg Psych 2003; 74: 1359–61CrossRef
111.
Mulley JC, Scheffer IE, Petrou S, et al. Channelopathies as a genetic cause of epilepsy. Curr Opin Neurol 2003; 16: 171–176PubMedCrossRef
112.
Baulac S, Huberfeld G, Gourfinkel-An I, et al. First evidence of GABAA receptor dysfunction in epilepsy: a mutation in the γ2-subunit gene. Nat Genet 2001; 28: 46–8PubMed
113.
Wallace RH, Marini C, Petrou S, et al. Mutant GABAA receptor γ2-subunit in childhood absence epilepsy and febrile seizures. Nat Genet 2001; 28: 49–52PubMed
114.
Bowser DN, Wagner DA, Czajkowski C, et al. Altered kinetics and benzodiazepine sensitivity of a GABAA receptor subunit mutation (γ2-R43Q) found in human epilepsy. Proc Natl Acad Sci USA 2002; 99: 15170–5PubMedCrossRef
115.
Picard F, Bertrand S, Steinlein OK, et al. Mutated nicotinic receptors responsible for autosomal dominant nocturnal frontal lobe epilepsy are more sensitive to carbamazepine. Epilepsia 1999; 40(9): 1198–209PubMedCrossRef
116.
Guerrini R, Dravet C, Genton P, et al. Lamotrigine and seizure aggravation in severe myoclonic epilepsy. Epilepsia 1998; 39(5): 508–12PubMedCrossRef
117.
Bolstein D, Risch N. Discovering genotypes underlying human phenotypes: past successes for mendelian disease, future approaches for complex disease. Nat Genet Supplement 2003; 33: 228–37CrossRef
118.
Gambardella A, Manna I, Labate A, et al. GABA(B) receptor 1 polymorphism (G1465A) is associated with temporal lobe epilepsy. Neurology 2003; 60: 560–3PubMedCrossRef
119.
Salzmann A, Moulard B, Crespel A, et al. GABA 1 receptor polymorphism (G1465A) and temporal lobe epilepsy. Epilepsia 2005; 46(6): 931–3PubMedCrossRef
120.
Poirier J. Apolipoprotein E in animal models of CNS injury and in Alzheimer’s disease. Trends Neurosci 1994; 17: 525–30PubMedCrossRef
121.
Briellmann RS, Torn-Broers Y, Busuttil BE, et al. APOE epsilon4 genotype is associated with an earlier onset of chronic temporal lobe epilepsy. Neurology 2000; 55: 435–7PubMedCrossRef
122.
Stogmann E, Zimprich A, Baumgartner C, et al. A functional polymorphism in the prodynorphin gene promoter is associated with temporal lobe epilepsy. Ann Neurol 2002 Feb; 51: 260–3PubMedCrossRef
123.
Tilgen N, Rebstock J, Horvath S, et al. Prodynorphin gene promoter polymorphism and temporal lobe epilepsy. Ann Neurol 2003; 53(2): 280–2PubMedCrossRef
124.
Kanemoto K, Kawasaki J, Miyamoto T, et al. Interleukin (IL)β, IL-1α, and IL-1 receptor antagonist gene polymorphisms in patients with temporal lobe epilepsy. Ann Neurol 2000 May; 47(5): 571–4PubMedCrossRef
125.
Heils A, Haug K, Kunz WS, et al. Interleukin-1beta gene polymorphism and susceptibility to temporal lobe epilepsy with hippocampal sclerosis. Ann Neurol 2000; 48(6): 948–50PubMedCrossRef
126.
Tsai F-J, Hsieh Y-Y, Chang C-C, et al. Polymorphisms for interleukin 1beta exon 5 and interleukin 1 receptor antagonist in Taiwanese children with febrile convulsions. Arch Pediatr Adolesc Med 2002; 156: 545–8PubMed
127.
Coenen AM, Drinkenburg WH, Inoue M, et al. Genetic models of absence epilepsy, with emphasis on the WAG/Rij strain of rats. Epilepsy Res 1992 Jul; 12(2): 75–86PubMedCrossRef
128.
Przewlocka B, Lason W, Turchan J, et al. Anatomical and functional aspects of mu opioid receptors in epileptic WAG/Rij rats. Epilepsy Res 1998 Jan; 29(2): 167–73PubMedCrossRef
129.
Han SH, Cho YW, Kim CJ, et al. Mu-opioid agonist-induced activation of G-protein-coupled inwardly rectifying potassium current in rat periaqueductal gray neurons. Neuroscience 1999 Apr; 90(1): 209–19PubMedCrossRef
130.
Sander TH, Berlin W, Gscheidel N, et al. Genetic variation of the human μ-opioid receptor and susceptibility to idiopathic absence epilepsy. Epilepsy Res 2000; 39: 57–61PubMedCrossRef
131.
Bond C, LaForge KS, Tian M, et al. Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction. Proc Natl Acad Sci USA 1998 Aug; 95(16): 9608–13PubMedCrossRef
132.
Wang JB, Imai Y, Eppler CM, et al. Mu opiate receptor: cDNA cloning and expression. Proc Natl Acad Sci USA 1993 Nov; 90(21): 10230–4PubMedCrossRef
133.
Duncan S, Mercho S, Lopes-Cendes I, et al. Repeated neural tube defects and valproate monotherapy suggest a pharmacogenetic abnormality. Epilepsia 2001; 42(6): 750–3PubMedCrossRef
134.
MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 1991 Jul 20; 338: 131–7CrossRef
135.
Hishida R, Nau H. VPA-induced neural tube defects in mice: I. Altered metabolism of sulfur amino acids and glutathione. Teratog Carcinog Mutagen 1988; 18(2): 49–61
136.
Ehlers K, Elmazar MA, Nau H. Methionine reduces the valproic acid induced spina bifida rate in mice without altering valproic acid kinetics. J Nutr 1996; 126: 67–75PubMed
137.
Molloy AM, Daly S, Mills JL, et al. Thermolabile variant of 5,10-methylenetetrahydrofolate reductase associated with low red cell folates: implications for folate intake recommendations. Lancet 1997; 349: 1591–3PubMedCrossRef
138.
Christensen B, Arbour L, Tran P. Genetic polymorphisms in MTHFR and methionine synthase folate levels in red cells and risk of neural tube defects. Am J Med Genet 1999; 84: 151–7PubMedCrossRef
139.
Finnell RH, Wlodarczyk BC, Craig JC, et al. Strain-dependent alterations in the expression of folate pathway genes following teratogenic exposure to valproic acid in a mouse. Am J Med Genet 1997; 70: 303–11PubMedCrossRef
140.
Gennis MA, Vemuri R, Burns EA, et al. Familial occurrence of hypersensitivity to phenytoin. Am J Med 1991; 91: 631–4PubMedCrossRef
141.
Fischer PR, Shigeoka AO. Familial occurrence of Stevens-Johnson syndrome. Am J Dis Child 1983; 137(9): 914–6PubMed
142.
Roujeau J-C, Stern RS. Severe cutaneous adverse reactions to drugs. N Engl J Med 1994; 331(19): 1272–85PubMedCrossRef
143.
Roujeau JC. Pharmacogénétique des réactions médicamenteuses cutanées graves. Revue française d’allergologie et d’immunologie clinique. 2003; 43: 211–5CrossRef
144.
Pirmohamed M, Lin K, Chadwick D, et al. TNFα promoter region gene polymorphisms in carbamazepine-hypersensitive patients. Neurology 2001; 56: 890–6PubMedCrossRef
145.
Schnyder B, Burkhart C, Schnyder-Frutig K, et al. Recognition of sulfamethoxazole and its reactive metabolites by drug-specific CD4+ T cells from allergic individuals. J Immunol 2000; 164: 6647–54PubMed
146.
Wen-Hung C, Shuen-Iu H, Hong-Shang H, et al. A marker for Stevens-Johnson syndrome. Nature 2004 Apr; 428: 486CrossRef
147.
Schlosstein L, Terasaki PI, Bluestone R, et al. High association of an HLA-A antigen, W27, with ankylosing spondylitis. N Engl J Med 1973; 288(14): 704–6PubMedCrossRef
148.
Martin ER, Lai EH, Gilbert JR, et al. S Ping away at complex diseases: analysis of single-nucleotide polymorphisms around APOE in Alzheimer disease. Am J Hum Genet 2000; 67(2): 383–94PubMedCrossRef
149.
McCarthy LC, Bhatti SM, Bird MI, et al. Single-nucleotide polymorphism alleles in the insulin receptor gene are associated with typical migraine [published erratum appears in Genomics 2002; 79(2): 271]. Genomics 2001; 78(3): 135–49PubMedCrossRef
150.
Hewett D, Samulesson L, Polding J, et al. Identification of a psoriasis susceptibility candidate gene by linkage disequilibrium mapping with a localized single nucleotide polymorphism map. Genomics 2002; 79(3): 305–14PubMedCrossRef
151.
Roses AD, Saunders AM. APOE is a major susceptibility gene for Alzheimer’s disease. Curr Opin Biotechnol 1994; 5(6): 663–7PubMedCrossRef
152.
Poirier J, Delisle MC, Quirion R, et al. Apolipoprotein E4 allele as a predictor of cholinergic deficits and treatment outcome in Alzheimer disease. Proc Natl Acad Sci USA 1995; 92: 12260–4PubMedCrossRef
153.
Evans WE, McLeod HL. Pharmacogenomics: drug disposition, drug targets, and side effects. N Engl J Med 2003; 248(6): 538–49
154.
The International SNP Map Working Group. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 2001; 409: 928–33CrossRef
155.
156.
Roses AD. Pharmacogenetics place in modern medical science and practice. Life Sci 2001; 70: 1471–80CrossRef
Metadata
Title
Various Pharmacogenetic Aspects of Antiepileptic Drug Therapy
A Review
Authors
Dr Michael W. Mann
Gerard Pons
Publication date
01-02-2007
Publisher
Springer International Publishing
Published in
CNS Drugs / Issue 2/2007
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI
https://doi.org/10.2165/00023210-200721020-00005

Other articles of this Issue 2/2007

CNS Drugs 2/2007 Go to the issue

Review Article

Lack of Insight in Schizophrenia

Adis Spotlight

Spotlight on Methylphenidate Controlled-Delivery Capsules(Equasym™XL, Metadate CD™) in the Treatment of Children and Adolescents with Attention-Deficit Hyperactivity Disorder

Original Research Article

Spectral Frequency Index Monitoring During Propofol-Remifentanil and Propofol-Alfentanil Total Intravenous Anaesthesia

Therapy in Practice

Monitoring the Safe Use of Clozapine

Therapy in Practice

Pharmacological Treatment of the Psychosis of Alzheimer’s Disease

Leading Article

Treatment Strategies After a Single Seizure