TABLE 4

CYP2A6 alleles and their effect on nicotine metabolism

Allele^a	Nucleotide Changes in the Gene	Effect	Activity Towards Nicotine (or Other Substrates)^b		References
Allele^a	Nucleotide Changes in the Gene	Effect	In Vivo	In Vitro	References
CYP2A6^1A*	None		Normal	Normal	Yamano et al., 1990
CYP2A6^1B1* (formerly CYP2A6^1B,* has also been called CYP2A6^1E*)	Gene conversion in the 3′ flanking region		Increased?		Nakajima et al., 2001; Yoshida et al., 2003; Pitarque et al., 2004
CYP2A6^1B2* (formerly CYP2A6^1B*)	-1013 A → G; gene conversion in the 3′ flanking region				Oscarson et al., 1999b; Ariyoshi et al., 2000; Pitarque et al., 2004
CYP2A6^1B3* (formerly CYP2A6^1C*)	-395 G → A; gene conversion in the 3′ flanking region				Kiyotani et al., 2002
CYP2A6^1C*	See CYP2A6^1B3*
CYP2A6^1D*	-1013 A → G			(Decreased transcription)	Pitarque et al., 2004
CYP2A6^1E*	See CYP2A6^1B1*
CYP2A6^1F*	5717 C → T				Nakajima et al., 2004
CYP2A6^1G*	5717 C → T; 5825 A → G				Nakajima et al., 2004
CYP2A6^1H*	-745 A → G	Disruption of a CCAAT box		(Decreased transcription)	Von Richter et al., 2004
CYP2A6^1J*	-1013 A → G; -745 A → G				Von Richter et al., 2004
CYP2A6^1X2*		CYP2A6 gene duplication	Increased		Rao et al., 2000
CYP2A6^2*	1799 T → A	L160H	None	(None)	Yamano et al., 1990; Benowitz et al., 2001
CYP2A6^3* ^c	CYP2A6/CYP2A7 hybrid				Fernandez-Salguero et al., 1995
CYP2A6^4A-D* ^d	CYP2A6 deleted	CYP2A6 deleted	None	(None)	Nunoya et al., 1998; Kitagawa et al., 1999; Nakajima et al., 2000; Kwon et al., 2001; Zhang et al., 2002
CYP2A6^5*	6582 G → T	G479V	(None)	(None)	Oscarson et al., 1999a
CYP2A6^6*	1703 G → A	R128Q		(Decreased)	Kitagawa et al., 2001
CYP2A6^7*	6558 T → C; gene conversion in the 3′ flanking region	I471T	Decreased	Decreased	Ariyoshi et al., 2001; Xu et al., 2002b; Yoshida et al., 2002
CYP2A6^8*	6600 G → T; gene conversion in the 3′ flanking region	R485L	Decreased		Yoshida et al., 2003
CYP2A6^9*	-1013 A → G; -48 T → G; 51 G → A	Disruption of the TATA box	Decreased	(Decreased)	Pitarque et al., 2001; Yoshida et al., 2003; Von Richter et al., 2004
CYP2A6^10*	6558 T → C; 6600 G → T; gene conversion in the 3′-flanking region	I471T; R485L	Decreased		Unpublished data; Yoshida et al., 2002, Xu et al., 2002b
CYP2A6^11*	3391 T → C	S224P	(Decreased)	(Decreased)	Daigo et al., 2002
CYP2A6^12*	Exons 1–2 of CYP2A7 origin; exons 3–9 of CYP2A6 origin	10 amino acid substitutions	(Decreased)	(Decreased)	Oscarson et al., 2002
CYP2A6^13*	-48 T → G; 13 G → A	G5R			Kiyotani et al., 2002
CYP2A6^14*	86 G → A	S29N			Kiyotani et al., 2002
CYP2A6^15*	-48 T → G; 22 C → T; 2134 A → G	K194E			Kiyotani et al., 2002
CYP2A6^16*	2161 C → A	R203S			Kiyotani et al., 2002
CYP2A6^17*	209 C → T; 1779 G → A; 4489 C → T; 5065 G → A; 5163 G → A; 5717 C → T; 5825 A → G	V365M	Decreased	Decreased	Fukami et al., 2004

↵ a Nomenclature according to the Human Cytochrome P450 (CYP) Allele Nomenclature Committee (see: http://www.imm.ki.se/CYPalleles/, accessed December 4, 2004)
↵ b Activity toward other substrates given in parentheses, if activity toward nicotine is unknown
↵ c CYP2A6^*3 may be an artefact (Oscarson et al., 1998)
↵ d CYP2A6^*4A and CYP2A6^*4C are identical. Other CYP2A6^*4 alleles are slightly different but all result in deletion of the whole CYP2A6 gene (Ariyoshi et al., 2002b)