Genetic Analyses For Epidemiologic Studies Of Respirator

该项目为斯蒂芬妮·伦敦通过流行病学分部进行的流行病学研究提供遗传分析。流行病学项目在以下Z01项目编号-49017、49019、43012下引用和描述。简而言之，这些是肺癌(49017)、儿童呼吸系统疾病(49019，包括哮喘和肺功能受损)和成人非恶性呼吸系统疾病(43012)的流行病学研究。这些研究正在不同的族裔群体中进行。对肺癌的研究在非洲裔美国人、高加索人和上海的中国人中进行。儿童呼吸系统疾病的研究包括南加州、武汉、中国和墨西哥城的人群，非恶性呼吸系统疾病的研究在新加坡。这些国际人群之所以令人感兴趣，是因为哮喘的发病率差异很大。我们正在寻求一种候选的基因方法，根据基因的功能选择与哮喘潜在相关的基因的多态，在某些情况下，选择与哮喘相关的连锁区中的位置。重点是功能上有意义的多态。我们已经通过环境基因组计划提名了用于多态筛选的基因。一旦这些候选基因被筛选，我们将跟踪流行病学研究中的任何多态以及筛选功能意义。在过去的一年里，该实验室一直致力于建立实验室，并聘用/培训一名技术人员和博士后。我们在道格·贝尔的帮助下完成了这项工作。我们已经完成了在肺癌研究中涉及DNA修复的三个多态性的实验室分析-两个在XRCC1基因中，一个在XPD基因中。我们将检查更多的肺癌候选基因。关于哮喘，我们目前正在建立对最近描述的IL-13基因中似乎影响功能的两个多态的分析。一个位于-1055的启动子区域，另一个位于编码区(外显子4)，导致氨基酸替换(Arg 130Gln)。我们将在明年寻找更多哮喘的候选基因。除了基于之前的连锁结果的哮喘候选外，我们还有兴趣检查TLR4基因的多态性，这些基因似乎与内毒素、臭氧和颗粒的反应有关，这种暴露在墨西哥城和武汉的研究以及墨西哥城的研究臭氧中都是很高的。墨西哥城的臭氧水平是北美最高的。涉及的实验室技术包括RFLP/PCR法和TaqMan PCR法。

This project provides genetic analyses for epidemiologic studies being conducted by Stephanie London through the epidemiology branch. The epidemiologic projects are referencedand 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 are 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.