Genetic analyses for epidemiology of respiratory disease

呼吸道疾病流行病学的遗传分析

• 批准号: 6413419
• 负责人: STEPHANIE JOAN LONDON
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6413419
• 关键词: asthma; clinical research; genetic polymorphism; human subject; lung; molecular genetics; polymerase chain reaction; respiratory disorder; respiratory disorder epidemiology; respiratory function

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.

项目摘要：该项目为斯蒂芬妮·伦敦通过流行病学分支进行的流行病学研究提供了遗传分析。流行病学项目在以下Z01项目编号-49017、49019、43012中进行了描述。简而言之，这些是肺癌的流行病学研究（49017），儿童呼吸道疾病，49019（49019，包括肺部和非肺功能障碍）和成人非肿瘤症状疾病） （43012）。这些研究是在各个种族中进行的。肺癌的研究是在非洲裔美国人，高加索人和上海的中国人。儿童期呼吸道疾病的研究包括南加州，武汉中国和墨西哥城的人口以及非恶性呼吸道疾病的研究在新加坡。这些国际人口具有利益，因为哮喘的发生率差异很大。我们正在追求候选基因 在基因中选择与哮喘的功能相关的基因中的多态性的方法，在某些情况下，在某些情况下，它们在哮喘的连锁区域中的额外位置。重点是功能上重要的多态性。我们提名了通过环境基因组项目筛选多态性的基因。一旦筛选了这些候选基因，我们将跟进流行病学研究中的任何多态性 筛选功能意义。过去的一年一直致力于建立实验室和招聘/培训技术人员和博士后。我们在道格·贝尔（Doug Bell）的帮助下做到了这一点。我们已经完成了肺癌研究中参与DNA修复的三种多态性的实验室分析 - XRCC1基因中的两个，一个在XPD基因中。我们将检查其他肺癌候选基因。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测定法似乎影响了功能。一个在-1055的启动子区域，一个在编码区域（外显子4）导致氨基酸取代（ARG 130GLN）。明年，我们将追求其他哮喘的候选基因。除了基于先前的连锁结果的哮喘候选物外，我们有兴趣检查TLR4基因中的多态性，这些多态性似乎与内毒素，臭氧和颗粒有关，这是墨西哥城和武汉研究的较高暴露，对于墨西哥城研究，墨西哥城研究很高。墨西哥城在北美的臭氧水平最高。涉及的实验室技术包括RFLP/PCR和Taqman PCR。