Pharmacogenetics of nicotine replacement therapy in New Zealand
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%). This trend has contributed to a higher smoking-related death rate in Maori (~31%) compared to the national average (~17%).
Variation in nicotine metabolic rate is thought to influence a smoker's risk of becoming addicted, cigarette consumption and ability to quit, as well as risk of diseases such as heart disease, lung cancer and COPD. Nicotine is primarily metabolised to cotinine by the liver enzyme cytochrome P450 2A6 (CYP2A6). The activity of this enzyme, and therefore nicotine metabolism, is under significant genetic control (heritability ~%60).
Our studies are focusing on measuring CYP2A6 activity in smokers by genotype and nicotine metabolites to determine whether a) there are ethnic differences in nicotine metabolic rate in NZ and b) if nicotine metabolic rate influences ability to quit smoking using nicotine replacement therapy (NRT).
Our latest unpublished data provides evidence that a) self-reported Maori ancestry correlates strongly with genetically reduced CYP2A6 activity (P = 0.006) and b) that smokers attempting to quit using NRT may be more successful if they receive a dosage that matches their pre-quit nicotine levels (preliminary data). These findings suggest that a) reporting Maori ancestry may be a useful genetic proxy for clinical prescription of NRT in NZ and b) CYP2A6 activity may be an important underlying factor for NRT dosage matching in smokers attempting to quit. The overall goal of this new pharmacogenetic research is to contribute to more personalised NRT, and in turn help reduce the high smoking prevalence and associated disease in NZ.