Innate Immunity in Heart, Lung and Blood Disease

Asthma, chronic obstructive pulmonary disease, myocardial infarction, and deep venous thrombosis are common, complex diseases associated with significant morbidity and mortality. An important factor in the pathogenesis of all four conditions is the development of a local inflammatory process in which the innate immune system plays a major role. The NHLBI University of Arizona/Brigham and Women's Hospital Innate Immunity PGA will use SNP variation discovery technologies to screen for polymorphisms in 50 genes known to be directly or indirectly related to the innate immune response. We will then genotype a sample of individuals of Hispanic, non-Hispanic White, and African American ethnicity for a proportion of the newly discovered polymorphisms. Association analyses will be performed to identify SNPs most likely to be involved in the determination of asthma, chronic obstructive pulmonary disease, myocardial infarction and deep venous thrombosis and to examine ethnic diversity. We will promptly disseminate the information on ethnic-specific and phenotype-specific distribution of the polymorphisms under study on a web site. Concurrently, we will develop a training program that will allow individuals with varying levels of knowledge and experience to become acquainted with modern genetic techniques. This training program will particularly stress the fields of high throughput sequencing and genotyping; study design, data handling and data analysis in genetic epidemiology; and ethical issues in population genetics.

• Identification of SNPs in candidate genes involved in the innate immunity response and that may have relevance to heart, lung, and blood diseases.
• Allele frequencies of these SNPs in a representative sample of Hispanics, non-Hispanics Whites, and African Americans
• Preliminary results of analyses of the association between the newly discovered SNPs and asthma, chronic obstructive pulmonary disease, myocardial infarction, and deep venous thrombosis
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