CYP2A6 alleles and their effect on nicotine metabolism
Allelea | Nucleotide Changes in the Gene | Effect | Activity Towards Nicotine (or Other Substrates)b | References | |
---|---|---|---|---|---|
In Vivo | In Vitro | ||||
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CYP2A6*10 | 6558 T → C; 6600 G → T; gene conversion in the 3′-flanking region | I471T; R485L | Decreased | Unpublished data; Yoshida et al., 2002, Xu et al., 2002b | |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)