رسالة جامعية

Association of Three Biomarkers of Nicotine as Pharmacogenomic Indices of Cigarette Consumption in Military Populations

التفاصيل البيبلوغرافية
العنوان: Association of Three Biomarkers of Nicotine as Pharmacogenomic Indices of Cigarette Consumption in Military Populations
المؤلفون: Matcham, William Arthur
Advisors: Ahijevych, Karen
الملخص: Tobacco-related diseases have reached epidemic proportions. There is no risk-free level of tobacco exposure. In the United States, tobacco use is the single largest preventable cause of death and disease in both men and women. Cigarette smoking alone accounts for approximately 443,000 deaths per year (one fifth of total US deaths) costing a staggering $193 billion per year in avoidable healthcare expenses and lost productivity. Literature shows military populations have rates of tobacco use two to three times higher than the civilian population. Military personnel returning from deployment in conflict areas can exceed 50% smoking prevalence. Research shows that genetic factors account for 40-70% of variation in smoking initiation and 50-60% of variance in cessation success. In the U.S., tobacco is responsible for more deaths than alcohol, AIDS, car accidents, illegal drugs, murders and suicides combined.This descriptive, cross-sectional study examined three of the biological markers used in tobacco research: the a4ß2 brain nicotinic receptors (nAChR) that contribute to genetic risk for nicotine dependence, nicotine metabolite ratio (NMR) as a phenotypic marker for CYP2A6 activity, and bitter taste phenotype (BTP) to determine their impact on cigarette consumption in military populations. Sociodemographic and military variables were examined to determine if they impacted biomarker relationships. The availability of reliable biomarkers will facilitate development of personalized smoking cessation therapies for military personnel.The first chapter reviewed the state of the science related to the nicotine metabolism in the human body, nicotine acetylcholine receptor in the brain and perception of bitter taste as they apply to nicotine and smoking research. An in-depth description of CYP2A6 genetics and phenotype measurement is presented including identification of gene variation, problems with standardizing genetic testing, naming conventions and classifications. The function of nicotine acetylcholine receptor is reviewed with a detailed description of the rs16969968 single nucleotide polymorphism used to characterize risk of nicotine dependence. Bitter taste phenotype is reviewed in the context of cigarette smoking.The second chapter provided an overview of recruitment techniques used with military personnel. A timeline of recruitment activities was followed by a review of internal and external environmental influences that affected recruitment. An analysis of lessons learned is presented with a summary of strategies to overcome recruitment challenges which can be applied to broader populations than military personnel.The third chapter presents the method and procedures of the study. Inadequate subject accrual resulted in only 15 of the expected 160 participants completing the study. The results of the study were analyzed with biserial and Kendall’s tau coefficients but overall were not significant. The planned prediction modeling and interaction analysis could not be conducted due to low participant enrollment. Results did show some interesting relationships between military and sociodemographic variables. This study has provided valuable data to characterize the diverse individuals in the military and provides evidence for inclusion of this important group in future studies.
URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1401294932Test
قاعدة البيانات: OpenDissertations