Some, but by no means most, of the individual variability in the rate at which nicotine is metabolized can be explained by CYP2A6 SNPs. Generally, smokers whose bodies rapidly metabolize nicotine will smoke more cigarettes, take in more cigarette smoke, and be more resistant to kicking the habit than slower metabolizers.
The most common CYP2A6 allele, CYP2A6*1, is considered to give rise to a fast metabolizing phenotype. Four relatively common CYP2A6 alleles are associated with slower metabolizers; they are CYP2A6*2, CYP2A6*4, CYP2A6*9, and CYP2A6*12. [PMID 17112802] CYP2A6*5 is a rare non-functioning variant. [PMID 15993850] The CYP2A6*20 variant results in a truncated protein and no enzyme activity.
To be more precise, the estimated percentage of CYP2A6 activity by genotype is as follows:
- 100% activity (ie fast metabolizer): 2 copies of CYP2A6*1
- 60-70% activity: 1 copy of CYP2A6*1 and 1 copy of either CYP2A6*9 or CYP2A6*12
- 40-50% activity: either having:
- 2 copies of CYP2A6*9 or CYP2A6*12 (or one of each), or
- 1 copy of CYP1A6*1 and 1 copy of either CYP2A6*2 or CYP2A6*4
- under 40% activity: either having:
- 2 copies of CYP2A6*2 or CYP2A6*4 (or one of each), or
- 1 copy of (CYP2A6*2 or *4) plus one of (*9 or *12)
The more common CYP2A6 alleles can be defined based on the following variations: