Wood Smoke and Genetic Susceptibility to Asthma in An Honduran Population

描述(由申请人提供)：这是加州大学旧金山分校医学系、生物工程和治疗科学系助理教授Joshua Galanter博士的以患者为导向的职业发展奖(K23)的修订申请。加兰特博士在不同人群中哮喘的遗传流行病学和药物遗传学领域确立了自己作为年轻研究员的地位。拟议的K23奖项将为Galanter博士提供支持，以实现以下目标：(1)培养在不同人群中设计和实施临床研究的技能；(2)学习确定影响肺部健康的因素所需的流行病学和生物统计学方法；(3)开展哮喘的遗传流行病学研究；(4)获得在复杂疾病中进行遗传和基因-环境相互作用研究所需的专业知识；(5)培养评估固体燃料燃烧引起的室内空气污染暴露的技能；(6)发展独立的临床研究事业。为了实现这些目标，格兰特博士组建了一个导师团队，成员包括主要导师、加州大学旧金山分校哮喘遗传学实验室主任埃斯特班·冈萨雷斯·伯查德博士，以及几位共同导师和顾问，包括John Balmes、Neal Benowitz、Saunak Sen和Mario Castro博士。哮喘是一种复杂的疾病，是遗传因素和环境因素相互作用的结果。格兰特·S博士的研究将集中于在洪都拉斯奥兰乔市的一个普遍使用燃木炉的地区(目标1)，确定接触烧木柴炉子和哮喘以及严重程度和肺功能等相关特征之间的联系。他还将进行遗传关联分析，以确定该人群中的遗传风险因素和基因-环境相互作用(目标2)。这些可能有助于识别使个体对木材烟雾的影响敏感的基因变异，并阐明暴露在木材烟雾中可能导致哮喘的机制。最后，他将进行一项先导性研究，以获得哮喘受试者的广泛暴露和表型信息。他将测量家庭和个人常见空气污染物的暴露水平，确定暴露在烟雾中的炎性生物标志物和代谢物的特征，并进行详细的哮喘表型分析，包括彻底评估肺功能和对沙丁胺醇的反应，测量过敏反应标志物，以及基因表达分析(目标3)。

DESCRIPTION (provided by applicant): This is a revised application for a Patient Oriented Career Development Award (K23) for Dr. Joshua Galanter, an Assistant Professor in the Departments of Medicine and Bioengineering and Therapeutic Sciences at the University of California, San Francisco. Dr. Galanter is establishing himself as a young investigator in the fields of genetic epidemiology and pharmacogenetics of asthma in diverse populations. The proposed K23 award would provide Dr. Galanter with support to accomplish the following goals: (1) develop skills in the design and implementation of clinical studies in diverse populations; (2 learn the epidemiologic and biostatistical methods required to identify factors that influence lun health; (3) conduct research into the genetic epidemiology of asthma; (4) acquire the expertise required to perform genetic and gene-environment interaction studies in complex diseases; (5) foster skills to assess indoor air pollution exposures from solid fuel combustion; with an ultimat goal of (6) developing an independent clinical research career. In order to achieve these goals, Dr. Galanter has assembled a mentoring team comprised of a primary mentor, Dr. Esteban Gonz¿lez Burchard, Director of the Asthma Genetics Laboratory at UCSF, who conducts clinical research in asthma genetics, and several co-mentors and advisors, including Drs. John Balmes, Neal Benowitz, Saunak Sen, and Mario Castro. Asthma is a complex disease that results from the interplay between genetic and environmental factors. Dr. Galanter¿s research will focus on identifying a link between exposure to wood-burning stoves and asthma and related traits such as severity and lung function in a population in Olancho, Honduras, where the use of woodburning stoves is common (Aim 1). He will also perform a genetic association analysis to identify genetic risk factors and gene-environment interactions in this population (Aim 2). These may help identify genetic variants that confer individual susceptibility to the effects of wood smoke and elucidate the mechanism by which exposure to wood smoke could lead to asthma. Finally, he will perform a pilot study to obtain extensive exposure and phenotype information of asthmatic subjects. He will measure household and personal exposure levels of common air pollutants, characterize inflammatory biomarkers and metabolites of exposure to smoke, and perform a detailed asthma phenotyping, including thorough assessment of pulmonary function and response to albuterol, measurement of markers of allergic sensitization, and gene expression analyses (Aim 3).