Genetic analyses for epidemiology of respiratory disease

项目概要：该项目为Stephanie伦敦通过流行病学分支进行的流行病学研究提供遗传分析。在以下Z 01项目编号- 49017、49019、43012中引用了流行病学项目。简而言之，这些是肺癌（49017）、儿童呼吸道疾病（49019，包括哮喘和肺功能受损）和成人非恶性呼吸道疾病的流行病学研究 （43012）。这些研究是在各族裔群体中进行的。肺癌的研究是在非洲裔美国人，高加索人和上海，中国。儿童呼吸道疾病的研究包括南加州、中国武汉和墨西哥城的人群，非恶性呼吸道疾病的研究在新加坡进行。这些国际人群是令人感兴趣的，因为哮喘的发病率差异很大。我们正在寻找一个候选基因 方法选择基因多态性与潜在的相关性哮喘的基础上，他们的功能，并在某些情况下，额外的位置在区域的连锁哮喘。重点是功能上的显着多态性。我们已经通过环境基因组计划提名了用于筛选多态性的基因。一旦这些候选基因被筛选出来，我们将跟踪流行病学研究中的任何多态性， 筛选功能意义。过去的一年致力于建立实验室和雇用/培训技术人员和博士后。我们在道格·贝尔的帮助下做到了这一点。我们已经完成了对肺癌研究中涉及DNA修复的三种多态性的实验室分析-两种在XRCC 1基因中，一种在XPD基因中。我们将检测更多的肺癌候选基因。关于哮喘，我们目前正在建立 最近在IL-13基因中描述的两种多态性的分析似乎影响功能。一个位于启动子区-1055处，一个位于编码区（外显子4），导致氨基酸取代（Arg 130 Gln）。我们将在明年寻找更多的哮喘候选基因。除了基于先前连锁结果的哮喘候选者之外，我们感兴趣的是检查Tlr 4基因的多态性，这些多态性似乎参与了对内毒素、臭氧和颗粒物的反应，墨西哥城和武汉研究的暴露量很高，而墨西哥城研究的暴露量很高，臭氧。墨西哥城是北美臭氧含量最高的城市。所涉及的实验室技术包括RFLP/PCR和TaqMan PCR。

Project Summary: This project provides genetic analyses for epidemiologic studies being conducted by Stephanie London through the epidemiology branch. The epidemiologic projects are referenced described under the following Z01 project numbers - 49017, 49019, 43012. In brief, these are epidemiology studies of lung cancer (49017), childhood respiratory illness (49019, including asthma and impaired lung function) and adult nonmalignant respiratory illness (43012). These studies are being conducted in various ethnic groups. The studies of lung cancer are in African-Americans, Caucasians, and Shanghai, Chinese. The studies of childhood respiratory illness include populations in Southern California, Wuhan China and Mexico City and the study of nonmalignant respiratory disease is in Singapore. These international populations are of interest because rates of asthma vary widely. We are pursuing a candidate gene approach selecting polymorphisms in genes with potential relevance to asthma based on their function and, in some instances additional their location in regions of linkage for asthma. The emphasis is on functionally significant polymorphisms. We have nominated genes for screening for polymorphisms through the Environmental Genome Project. Once these candidate genes be screened, we would follow-up any polymorphisms in the epidemiologic studies as well as screening for functional significance. This past year has been devoted to setting up the laboratory and hiring/training a technician and postdoc. We have done this with the help of Doug Bell. We have completed laboratory analysis of three polymorphisms involved in DNA repair in the lung cancer study - two in the XRCC1 gene and one in the XPD gene. We will be examining additional lung cancer candidate genes. With respect to asthma, we are currently establishing assays for two polymorphisms recently described in the IL-13 gene which appear to influence function. One is in the promoter region at -1055 and one in the coding region (exon 4) leads to an amino acid substitution (Arg 130Gln). We will be pursuing additional candidate genes for asthma in this next year. In addition to asthma candidates based on previous linkage results, we are interested in examining polymorphisms in the Tlr4 gene that appear to involved in response to endotoxin, ozone and particles , an exposure which is high for both the Mexico City and Wuhan studies, and for the Mexico City study, ozone. Mexico City has the highest ozone levels in North America. The laboratory techniques involved include RFLP/PCR and TaqMan PCR.