Ethnic differences in nicotine metabolic rate among New Zealanders.
OBJECTIVE
To estimate (a) the prevalence of gene variants associated with slow nicotine metabolism in the general Maori population and (b) nicotine intake and metabolic rate in Maori and European smokers.


METHODS
The procedure involved (a) genotyping 85 Maori participants for cytochrome P-450 2A6 (CYP2A6) gene variants, which are associated with reduced nicotine metabolic rate (ie CYP2A6*9 and *4); and (b) measuring salivary cotinine (COT) and trans-3'-hydroxycotinine (3-HC) as biomarkers of nicotine intake and metabolic rate in 12 female smokers from the Hawke's Bay Region (6 Maori and 6 European).


RESULTS
(a) The frequencies of the slow nicotine metabolising variants, CYP2A6*9 and *4, were significantly higher in Maori compared to European (p<0.01). Indeed, the prevalence of the CYP2A6*9 variant in these Maori was among the highest in the world (approximately 20%). (b) In smokers, the Maori group had approximately 35% lower 3-HC:COT ratios indicating a reduced metabolic rate, as well as 2-fold lower cotinine levels per cigarette smoked, indicating reduced nicotine intake (p<0.05). The CYP2A6*9 allele was significantly more frequent in Maori smokers (70%) compared to Europeans (30%), p=0.03.


CONCLUSIONS
The findings of this study provide evidence that Maori are genetically slower nicotine metabolisers compared to Europeans. Although more research is required, this study may help explain ethnic differences in smoking initiation and may also have important implications for smoking cessation programs - since metabolic differences between groups with varying ancestry implies that different optimal dosages of nicotine replacement therapy may be required for successful quitting.
Lea
Rod
R
Institute of Environmental Science and Research, Wellington. Rod.Lea@esr.cri.nz
Benowitz
Neal
N
Green
Michael
M
Fowles
Jeff
J
Vishvanath
Anasuya
A
Dickson
Stuart
S
Lea
Marino
M
Woodward
Alistair
A
Chambers
Geoffrey
G
Phillips
David
D
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism; D065637:Cytochrome P-450 CYP2A6; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009520:New Zealand / Q000453:epidemiology; D009538:Nicotine / Q000378:metabolism*; D015995:Prevalence; D012463:Saliva / Q000378:metabolism; D012907:Smoking / Q000208:ethnology* / Q000235:genetics / Q000378:metabolism*; D044465:White People / Q000235:genetics* / Q000706:statistics & numerical data
D015415:Biomarkers; D009538:Nicotine; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6