A novel CYP2A6 allele (CYP2A6* 35) resulting in an amino-acid substitution (Asn438Tyr) is associated with lower CYP2A6 activity in vivo

Pharmacogenomics Journal

Volumn 9, Issue 4, 2009, Pages 274-282

  Al Koudsi, Nael ^a   Ahluwalia, Jasjit S ^b,c   Lin, Shih Ku ^d   Sellers, Edward M ^e,f   Tyndale, Rachel F ^a,f  

^a UNIVERSITY OF TORONTO   (Canada)

^b UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

^c UNIVERSITY OF MINNESOTA   (United States)

^d TAIPEI CITY HOSPITAL   (Taiwan)

^e Division of Clinical Pharmacology   (Canada)

^f CENTRE FOR ADDICTION AND MENTAL HEALTH   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE; ASPARAGINE; COTININE; CYTOCHROME P450 2A6; CYTOSINE; GUANOSINE; LEUCINE; NICOTINE; THYMINE; TYROSINE; VALINE;

AMINO ACID SUBSTITUTION; ARTICLE; ASIAN; CAUCASIAN; CONTROLLED STUDY; ENZYME ACTIVITY; ETHNICITY; GENE FREQUENCY; GENE IDENTIFICATION; GENETIC VARIABILITY; GENOTYPE; HAPLOTYPE; HUMAN; IN VITRO STUDY; IN VIVO STUDY; INTRON; NEGRO; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN STABILITY; RACE DIFFERENCE; SINGLE NUCLEOTIDE POLYMORPHISM; THERMOSTABILITY;

AFRICAN CONTINENTAL ANCESTRY GROUP; AMINO ACID SUBSTITUTION; ARYL HYDROCARBON HYDROXYLASES; ASIAN CONTINENTAL ANCESTRY GROUP; ENZYME STABILITY; EUROPEAN CONTINENTAL ANCESTRY GROUP; GENE FREQUENCY; HUMANS; KINETICS; NICOTINE; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 67849090529     PISSN: 1470269X     EISSN: 14731150     Source Type: Journal    
DOI: 10.1038/tpj.2009.11     Document Type: Article

References (50)

1. Benowitz NL. Clinical pharmacology of nicotine: Implications for understanding, preventing, and treating tobacco addiction. Clin Pharmacol Ther 2008; 83: 531-541.
2. Benowitz NL, Jacob III P. Metabolism of nicotine to cotinine studied by a dual stable isotope method. Clin Pharmacol Ther 1994; 56: 483-493.
3. Minematsu N, Nakamura H, Furuuchi M, Nakajima T, Takahashi S, Tateno H et al. Limitation of cigarette consumption by CYP2A6*4, *7 and *9 polymorphisms. Eur Respir J 2006; 27: 289-292.
4. Lerman C, Tyndale R, Patterson F, Wileyto EP, Shields PG, Pinto A et al. Nicotine metabolite ratio predicts efficacy of transdermal nicotine for smoking cessation. Clin Pharmacol Ther 2006; 79 600-608.
5. Schoedel KA, Hoffmann EB, Rao Y, Sellers EM, Tyndale RF. Ethnic variation in CYP2A6 and association of genetically slow nicotine metabolism and smoking in adult Caucasians. Pharmacogenetics 2004; 14: 615-626.
6. Patterson F, Schnoll RA, Wileyto EP, Pinto A, Epstein LH, Shields PG et al. Toward personalized therapy for smoking cessation: A randomized placebo-controlled trial of bupropion. Clin Pharmacol Ther 2008; 84: 320-325.
7. Nakajima M, Yamamoto T, Nunoya K, Yokoi T, Nagashima K, Inoue K et al Role of human cytochrome P4502A6 in C-oxidation of nicotine. Drug Metab Dispos 1996; 24: 1212-1217.
8. Messina ES, Tyndale RF, Sellers EM. A major role for CYP2A6 in nicotine C-oxidation by human liver microsomes. J Pharmacol Exp Ther 1997; 282: 1608-1614.
9. Nakajima M, Yamamoto T, Nunoya K, Yokoi T, Nagashima K, Inoue K et al Characterization of CYP2A6 involved in 3′-hydroxylation of cotinine in human liver microsomes. J Pharmacol Exp Ther 1996; 277: 1010-1015.
10. Dempsey D, Tutka P, Jacob III P, Allen F, Schoedel K, Tyndale RF et al. Nicotine metabolite ratio as an index of cytochrome P450 2A6 metabolic activity. Clin Pharmacol Ther 2004; 76: 64-72.
11. Yamanaka H, Nakajima M, Nishimura K, Yoshida R, Fukami T, Katoh M et al. Metabolic profile of nicotine in subjects whose CYP2A6 gene is deleted. Eur J Pharm Sci 2004; 22: 419-425.
12. Lea RA, Dickson S, Benowitz NL. Within-subject variation of the salivary 3HC/COT ratio in regular daily smokers: Prospects for estimating CYP2A6 enzyme activity in large-scale surveys of nicotine metabolic rate. J Anal Toxicol 2006; 30: 386-389.
13. Benowitz NL, Jacob III P, Jones RT, Rosenberg J. Interindividual variability in the metabolism and cardiovascular effects of nicotine in man. J Pharmacol Exp Ther 1982; 221: 368-372.
14. Benowitz NL, Swan GE, Jacob III P, Lessov-Schlaggar CN, Tyndale RF. CYP2A6 genotype and the metabolism and disposition kinetics of nicotine. Clin Pharmacol Ther 2006; 80: 457-467.
15. Mwenifumbo JC, Al Koudsi N, Ho MK, Zhou Q, Hoffmann EB, Sellers EM et al. Novel and established CYP2A6 alleles impair in vivo nicotine metabolism in a population of Black African descent. Hum Mutat 2008; 29: 679-688.
16. Mwenifumbo JC, Tyndale RF. Genetic variability in CYP2A6 and the pharmacokinetics of nicotine. Pharmacogenomics 2007; 8: 1385-1402.
17. Ariyoshi N, Sawamura Y, Kamataki T. A novel single nucleotide polymorphism altering stability and activity of CYP2a6. Biochem Biophys Res Commun 2001; 281: 810-814.
18. Nakajima M, Fukami T, Yamanaka H, Higashi E, Sakai H, Yoshida R et al Comprehensive evaluation of variability in nicotine metabolism and CYP2A6 polymorphic alleles in four ethnic populations. Clin Pharmacol Ther 2006; 80: 282-297.
19. Peamkrasatam S, Sriwatanakul K, Kiyotani K, Fujieda M, Yamazaki H, Kamataki T et al. In vivo evaluation of coumarin and nicotine as probe drugs to predict the metabolic capacity of CYP2A6 due to genetic polymorphism in Thais. Drug Metab Pharmacokinet 2006; 21: 475-484.
20. Xu C, Rao YS, Xu B, Hoffmann E, Jones J, Sellers EM et al. An in vivo pilot study characterizing the new CYP2A6*7, *8, and *10 alleles. Biochem Biophys Res Commun 2002; 290: 318-324.
21. Yoshida R, Nakajima M, Watanabe Y, Kwon JT, Yokoi T. Genetic polymorphisms in human CYP2A6 gene causing impaired nicotine metabolism. Br J Clin Pharmacol 2002; 54: 511-517.
22. Ho MK, Mwenifumbo JC, Al Koudsi N, Okuyemi KS, Ahluwalia JS, Benowitz NL et al. Association of CYP2A6 genotype and phenotype with smoking behaviors and treatment outcomes in African-American light smokers. Clin Pharmacol Ther 2009, advance online publication, 11 March 2009.
23. Iwahashi K, Waga C, Takimoto T. Whole deletion of CYP2A6 gene (CYP2A6AST;4C) and smoking behavior. Neuropsychobiology 2004; 49: 101-104.
24. Zhang X, Amemo K, Ameno S, Iwahashi K, Kinoshita H, Kubota T et al Lack of association between smoking and CYP2A6 gene polymorphisms in A Japanese population. Nihon Arukoru Yakubutsu Igakkai Zasshi 2001; 36: 486-490.
25. Tan W, Chen GF, Xing DY, Song CY, Kadlubar FF, Lin DX. Frequency of CYP2A6 gene deletion and its relation to risk of lung and esophageal cancer in the Chinese population. Int J Cancer 2001; 95: 96-101.
26. Lewis DF, Dickins M, Lake BG, Eddershaw PJ, Tarbit MH, Goldfarb PS. Molecular modelling of the human cytochrome P450 isoform CYP2A6 and investigations of CYP2A substrate selectivity. Toxicology 1999; 133: 1-33.
27. Yano JK, Hsu MH, Griffin KJ, Stout CD, Johnson EF. Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen. Nat Struct Mol Biol 2005; 12: 822-823.
28. Johnson EF, Stout CD. Structural diversity of human xenobiotic-metabolizing cytochrome P450 monooxygenases. Biochem Biophys Res Commun 2005; 338: 331-336.
29. Juvonen RO, Iwasaki M, Negishi M. Structural function of residue-209 in coumarin 7-hydroxylase (P450coh). Enzyme-kinetic studies and site-directed mutagenesis. J Biol Chem 1991; 266: 16431-16435.
30. Pitarque M, von Richter O, Rodriguez-Antona C, Wang J, Oscarson M, Ingelman-Sundberg M. A nicotine C-oxidase gene (CYP2A6) polymorphism important for promoter activity. Hum Mutat 2004; 23: 258-266.
31. von Richter O, Pitarque M, Rodriguez-Antona C, Testa A, Mantovani R, Oscarson M et al. Polymorphic NF-Y dependent regulation of human nicotine C-oxidase (CYP2A6). Pharmacogenetics 2004; 14: 369-379.
32. Salavaggione OE, Wang L, Wiepert M, Yee VC, Weinshilboum RM. Thiopurine S-methyltransferase pharmacogenetics: Variant allele functional and comparative genomics. Pharmacogenet Genomics 2005; 15: 801-815.
33. Wang L, Sullivan W, Toft D, Weinshilboum R. Thiopurine S-methyl-transferase pharmacogenetics: Chaperone protein association and allozyme degradation. Pharmacogenetics 2003; 13: 555-564.
34. Weinshilboum R, Wang L. Pharmacogenetics: Inherited variation in amino acid sequence and altered protein quantity. Clin Pharmacol Ther 2004; 75: 253-258.
35. Bandiera S, Weidlich S, Harth V, Broede P, Ko Y, Friedberg T. Proteasomal degradation of human CYP1B1: Effect of the Asn453Ser polymorphism on the post-translational regulation of CYP1B1 expression. Mol Pharmacol 2005; 67: 435-443.
36. Malaiyandi V, Lerman C, Benowitz NL, Jepson C, Patterson F, Tyndale RF. Impact of CYP2A6 genotype on pretreatment smoking behaviour and nicotine levels from and usage of nicotine replacement therapy. Mol Psychiatry 2006; 11: 400-409.
37. Fujieda M, Yamazaki H, Saito T, Kiyotani K, Gyamfi MA, Sakurai M et al. Evaluation of CYP2A6 genetic polymorphisms as determinants of smoking behavior and tobacco-related lung cancer risk in male Japanese smokers. Carcinogenesis 2004; 25: 2451-2458.
38. Mwenifumbo JC, Lessov-Schlaggar CN, Zhou Q, Krasnow RE, Swan GE, Benowitz NL et al. Identification of novel CYP2A6*1B variants: the CYP2A6*1B allele is associated with faster in vivo nicotine metabolism. Clin Pharmacol Ther 2008; 83: 115-121.
39. Hoffman SM, Fernandez-Salguero P, Gonzalez FJ, Mohrenweiser HW. Organization and evolution of the cytochrome P450 CYP2A-2B-2F subfamily gene cluster on human chromosome 19. J Mol Evol 1995; 41: 894-900.
40. Ahluwalia JS, Okuyemi K, Nollen N, Choi WS, Kaur H, Pulvers K et al The effects of nicotine gum and counseling among African American light smokers: A 2 × 2 factorial design. Addiction 2006; 101 883-891.
41. Mwenifumbo JC, Sellers EM, Tyndale RF. Nicotine metabolism and CYP2A6 activity in a population of black African descent: Impact of gender and light smoking. Drug Alcohol Depend 2007; 89: 24-33.
42. Ho MK, Mwenifumbo JC, Zhou Q, Hoffmann EB, Okuyemi K, Ahluwalia JS et al. CYP2A6 activity and its association with baseline smoking behaviors and treatment outcomes in a clinical trial of African-American light smokers. POS3-7, pg 87. In: Society for Research on Nicotine and Tobacco (SRNT 14th Annual Meeting): Portland, Oregon 2008.
43. Gillam EM, Aguinaldo AM, Notley LM, Kim D, Mundkowski RG, Volkov AA et al. Formation of indigo by recombinant mammalian cytochrome P450. Biochem Biophys Res Commun 1999; 265: 469-472.
44. Ho MK, Mwenifumbo JC, Zhao B, Gillam EM, Tyndale RF. A novel CYP2A6 allele, CYP2A6*23, impairs enzyme function in vitro and in vivo and decreases smoking in a population of Black-African descent. Pharmacogenet Genomics 2008; 18: 67-75.
45. Siu EC, Wildenauer DB, Tyndale RF. Nicotine self-administration in mice is associated with rates of nicotine inactivation by CYP2A5. Psychopharmacology (Berl) 2006; 184: 401-408.
46. Mwenifumbo JC, Sellers EM, Tyndale RF. The association of demographic characteristics with CYP2A6 mediated nicotine metabolism in a population of black African descent. Drug Alcohol Depend 2007; 89: 24-33.
47. Johnstone E, Benowitz N, Cargill A, Jacob R, Hinks L, Day I et al. Determinants of the rate of nicotine metabolism and effects on smoking behavior. Clin Pharmacol Ther 2006; 80: 319-330.
48. Nakajima M, Fukami T, Yamanaka H, Higashi E, Sakai H, Yoshida R et al Comprehensive evaluation of variability in nicotine metabolism and CYP2A6 polymorphic alleles in four ethnic populations. Clin Pharmacol Ther 2006; 80: 282-297.
49. Benowitz NL, Lessov-Schlaggar CN, Swan GE, Jacob III P. Female sex and oral contraceptive use accelerate nicotine metabolism. Clin Pharmacol Ther 2006; 79: 480-488.
50. Nakamura K, Ariyoshi N, Yokoi T, Ohgiya S, Chida M, Nagashima K et al CYP2D6.10 present in human liver microsomes shows low catalytic activity and thermal stability. Biochem Biophys Res Commun 2002; 293: 969-973.