TOPOGRAPHY AND GENETICS OF SMOKING AND NICOTINE DEPENDENCE IN AMERICAN INDIANS

北平原美洲印第安人(Al)的终生吸烟率超过50%，是 在美国总人口中的比例。更令人担忧的是，吸烟率实际上在 一些青年艾尔。我们的工作表明，阿尔茨海默氏症有一种独特的吸烟模式，其中阿尔茨海默氏症典型地吸烟 与大多数文化中的吸烟者相比，每天的香烟数量只有一半。我们还观察到 与前几代相比，最近几代阿尔茨海默氏症开始吸烟的年龄更小。然而，几乎没有人 严谨的科学研究考察了遗传和非遗传对烟草使用模式的影响。 在阿尔斯市。从2001年到2007年，我们进行了健康教育和研究(地球)研究， 它记录了北平原地球参与者目前的吸烟率为43%， 相比之下，西南部落的这一比例仅为19%。尽管这些差异可能是多因素的，但 从根本上说，吸烟的不同流行程度的原因是未知的。为了解释这些人口层面的 吸烟模式的差异，我们建议研究与以下因素有关的遗传和非遗传因素 在原始地球队列中的600名成员的分层随机抽样中的吸烟模式。我们的 最重要的假设是，ALS对吸烟和尼古丁依赖的易感性有 潜在的遗传成分，由于与多巴胺、5-羟色胺和尼古丁相关的基因变异 新陈代谢，以及心理社会、环境、文化和背景的影响。因此，我们的 具体目标是：1)在已知与吸烟有关的人之间进行候选基因关联研究 基因多态与吸烟状况；2)确定吸烟相关基因多态之间的关联 和吸烟者对尼古丁的依赖；以及3)检查特定的关联模式是否 吸烟状态和尼古丁依赖的多态因部落而有系统的不同。香烟 吸烟是美国可预防死亡的头号原因。这项拟议的研究将阐明 两个不同文化的Al部落群体的吸烟原因，最终确定干预的目标 个人和人口水平。通过了解特定的基因类型如何与非基因的 因素，使一些阿尔族部落群体容易吸烟，我们就可以开始影响吸烟和 与烟草有关的疾病是可以预防的，而且代价高昂。包括遗传信息的研究是独特的 阿尔茨海默病患者的吸烟行为，并可能在制定吸烟预防和戒烟计划方面发挥作用 在个人和社区层面。鉴于管理部落土地上烟草销售的独特法律，我们的 这些发现可能会对公共卫生产生无数的规划和政策相关影响。

Lifetime smoking prevalence in Northern Plains American Indians (Al) is above 50%, more than double the rate in the overall U.S. population. More worrisome is that smoking prevalence is actually increasing among some Al youth. Our work demonstrates that Als have a unique pattern of smoking, with Als typically smoking one-half the number of cigarettes per day compared with smokers in the majority culture. We also observed that more recent generations of Als are initiating smoking at younger ages than in past generations. Yet few rigorous scientific studies have examined the genetic and non-genetic influences on patterns of tobacco use in Als. From 2001 to 2007, we conducted the Education and Research Towards Health (EARTH) study, which documented the prevalence of current smoking among Northern Plains' EARTH participants was 43%, compared to only 19% in the Southwest tribe. Although these differences are likely multi-factorial, the reasons for such radically, different smoking prevalences are unknown. To explicate these population-level differences in smoking patterns, we propose to examine the genetic and non-genetic factors associated with cigarette smoking patterns in a stratified random sample of 600 members in the original EARTH cohort. Our overarching hypothesis is that the susceptibility of Als to smoking and nicotine dependence has an underlying genetic component, due to gene variants related to dopamine, serotonin, and nicotine metabolism, as well as psychosocial, environmental, cultural, and contextual influences. Therefore, our specific aims are to: 1) Perform candidate-gene association studies between known smoking-related polymorphisms and smoking status; 2) Determine the association between smoking-related polymorphisms and nicotine dependence among smoker; and 3) Examine whether the pattern of association of specific polymorphisms with smoking status and nicotine dependence varies systematically by tribe. Cigarette smoking is the number 1 cause of preventable death in the U.S.^¿ The proposed research will illuminate the causes of smoking in 2 culturally distinct Al tribal groups, ultimately to identify targets for intervention at the individual and population levels. By understanding how particular genotypes, in concert with non-genetic factors, predispose some Al tribal groups to smoking, we can begin to affect smoking and the multitude of preventable and costly tobacco-related diseases. Including genetic information is unique in studies of smoking behaviors among Als, and may have a role in shaping smoking prevention and cessation programs at the individual and community level. Given the unique laws governing tobacco sales on tribal lands, our findings could have a myriad of programmatic and policy-related public health impacts.