Pharmacogenetics of Nicotine Metabolism in Twins: Methods and Procedures

CYP2A6 genotype and the metabolism and disposition kinetics of nicotine

“…12 The overall rate of nonwhite participation in this study was below the 2000 US Census estimate for nonwhites residing in the San Francisco Bay Area; our data should not be generalized to nonwhite samples. 12 The overall rate of nonwhite participation in this study was below the 2000 US Census estimate for nonwhites residing in the San Francisco Bay Area; our data should not be generalized to nonwhite samples.…”

“…12 In a previous article we reported on the heritability of nicotine and cotinine clearances and the observation that heritability was affected to a relatively small extent by controlling for or eliminating subjects with any CYP2A6 gene variant. As part of a twin study of the heritability of nicotine metabolism, we administered intravenous nicotine and cotinine to 278 individual members of twin pairs who also underwent CYP2A6 genotyping.…”

Genetic and environmental influences on the ratio of 3′hydroxycotinine to cotinine in plasma and urine

“…Characterization of study participants has been reported elsewhere [17]. Generally, application of the exclusion criteria resulted in a younger, healthier study sample as compared to those who were deemed ineligible.…”

“…Exclusion Criteria— To minimize the effect of medical conditions and/or medication usage known to influence drug metabolism, individuals were excluded from participation if they met any of the following criteria: age of less than 18 years or older than 65 years; weight of more than 30% over ideal height-adjusted weight; pregnancy; the presence of any of the following conditions: use of drug metabolism-altering medications such as anticonvulsant drugs and barbiturates; uncontrolled hypertension or diabetes; a history of heart disease as indicated by self-report or history of bypass surgery, valve replacement, use of a pacemaker, or angioplasty procedures; Raynaud’s disease; chronic diseases such as cancer, liver, and kidney diseases, or asthma, that were not stable or were not in remission for at least 1 year; migraine headaches, anemia, abnormal blood sugar levels that were not well-controlled by medication, substance abuse and/or dependence (other than tobacco), psychiatric disorders that could limit study compliance or require the use of metabolism-altering psychotropic medications, positive HIV status, hepatitis B or C, history of vasovagal reactions, discomfort with venipuncture procedures, or a self-reported history of “difficult veins.” Because the study procedures could be seriously confounded or could lead to adverse events for the participants by the presence of the conditions described above, a three-tiered screening procedure (telephone, in-person, and in-hospital) was employed. All study procedures are described more completely elsewhere [17]. …”

Pharmacogenetics and Pharmacogenomics

“…The task of collecting appropriate related cohorts suffering from the same conditions and exposed to the same pharmacological agents is often not trivial (although has been demonstrated to be helpful in the case of nicotine Figure 15.1 Pharmacogenetic study design alternatives in a simplifi ed case, genotyping a single nucleotide polymorphism in a study population. metabolism [ Swan et al, 2004 ] and alcohol exposure [ Heath and Martin, 1994 ]). A priori genotyping may be used as inclusion criteria and in several models may be used to reduce study population, when equisize groups of genotype carriers (aa, aA, and AA) are randomized to treatment and subsequent analysis.…”