Ethnic differences in nicotine metabolic rate among New Zealanders

Aims 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 (~20%). (b) In smokers, the Maori group had ~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. In New Zealand (NZ), the prevalence of cigarette smoking is around 22% for the general population. However the smoking rates are markedly higher for Maori (~46%) compared to Europeans (20%) and, for reasons that are unclear, the rates for female Maori are among the highest in the world—52% nationally and up to 60% in some regions. 1 Extensive targeted campaigns for smoking cessation in the 1990s has led to a reduction in tobacco consumption in NZ, yet the high prevalence of smoking for Maori has not decreased. 1 High rates of smoking are associated with elevated rates of smoking-related diseases, and it has been estimated that smoking is responsible for around 30% of Maori deaths compared to about 17% nationally. 2 As these statistics emphasise, identifying the determinants of the high smoking prevalence in Maori and using this information to develop new targeted cessation strategies is of major public health importance in NZ.