This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Kawasaki Disease (KD) is an acute febrile illness of young children which is more common in Hawaii and Japan than any other location in the world. The disease is of unknown etiology although multiple clinical and epidemiologic features strongly suggest a microbial etiology. In the multi-ethnic environment of Hawaii the disease is significantly more common among children of Japanese ancestry than any other group. This fact suggests that susceptibility to the disease is genetically based.
The specific aim of the proposal is to explore the role of polymorphic alleles in susceptibility to KD and disease outcome. Hypothesis to be tested are: a) Alleles associated with cardiovascular health and immune activation pathways influence susceptibility to KD and risk of coronary artery damage due to KD b) Application of the transmission disequilibrium test (TDT) to triads of KD patients and their parents will identify candidate alleles that may predispose to KD, to coronary artery damage following KD, or to failure to respond to gamma globulin therapy.Study Population and Recruitment - The study population consists of: 1) KD patients and their biologic parents identified prospectively at the time of hospital admission for intravenous gamma globulin treatment and, 2) families whose children have had KD in the past. While inclusion of the KD patient and both biological parents (triad) is needed for application of the TDT (transmission disequilibrium test), KD subjects alone (singleton) or with a single biological parent (duo) will also be enrolled. A total of 500 to 1000 triads (500 to 1000 KD patients and 1,000 - 2000 parents, 1,500 3000 total subjects) will be enrolled from all sites. The Honolulu Site is expected to provide 200 triads. The other study sites include UCSD, Harvard and Northwestern University Medical School.Specimen and Data Collection: A DNA sample (either blood or buccal cells) will be collected from each participant. Parents/adult KD patients will complete a patient information sheet; medical history relating to KD, sequelae, and treatment response will be obtained from the subject's medical records and will be recorded on a data collection form.Specimen Transport and Testing - Blood, cheek swabbings or mouthwash identified only by study ID# will be sent to Dr. Burns' laboratory at UCSD where the DNA is extracted and analyzed. Data analysis: We are proposing to collect data on 148 candidate polymorphisms from 500 triads of KD patients and their parents. The ability to identify significant associations between KD susceptibility and a given polymorphism will depend on the allele frequency in the population, as well as the risk it confers on an individual.
Showing the most recent 10 out of 245 publications
