Overview of the pharmacogenomics of cigarette smoking.
Cigarette smoking increases the risk of numerous health problems, including cancer, cardiovascular and pulmonary disorders, making smoking the leading cause of preventable death in the world. Nicotine is primarily responsible for the highly addictive properties of cigarettes. Although the majority of smokers express a desire to quit, few are successful in doing so. Twin and family studies have indicated substantial genetic contributions to smoking behaviors. One major research focus has been to elucidate the specific genes involved; this has been accomplished primarily through genome-wide linkage analyses and candidate gene association studies. Much attention has focused on genes involved in the neurotransmitter pathways for the brain reward system and genes altering nicotine metabolism. This paper reviews the current state of knowledge for genetic factors implicated in smoking behaviors, and examines how genetic variations may affect therapeutic outcomes for drugs used to assist smoking cessation.
Ho
M K
MK
Centre for Addiction and Mental Health, Department of Pharmacology, University of Toronto, Toronto, Canada.
Tyndale
R F
RF
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D016739:Behavior, Addictive / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control*; D065637:Cytochrome P-450 CYP2A6; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D009538:Nicotine / Q000378:metabolism*; D018579:Patient Selection; D020641:Polymorphism, Single Nucleotide; D011950:Receptors, Cholinergic / Q000378:metabolism; D011954:Receptors, Dopamine / Q000235:genetics; D012107:Research Design; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D012907:Smoking / Q000235:genetics* / Q000378:metabolism; D016540:Smoking Cessation / Q000379:methods*; D000074606:Smoking Prevention; D016896:Treatment Outcome; D014365:Tryptophan Hydroxylase / Q000235:genetics
D050483:Dopamine Plasma Membrane Transport Proteins; D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D009538:Nicotine; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6; D014365:Tryptophan Hydroxylase; D004298:Dopamine