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.Diabetic Retinopathy (retinal eye disease, DR) is the leading cause of blindness in people aged 20-74 years in the United States. Although retinopathy is more common in type 1 diabetes, the majority of new cases are due to type 2 diabetes (T2DM). The socioeconomic cost of DR is expected to escalate with the increasing prevalence of T2DM due to the aging of the American society and the rapid growth of minority populations with predilection to T2DM and its complications. Severe forms of DR occur only, however, in approximately one-third of patients, i.e., a subgroup that appears to be genetically predisposed to progressive disease. Although other factors also play a role in the development of DR, such as glucose control and high blood pressure, this proposal will focus on studying genetics of DR. The Hispanic population will be studied in this grant because Latinos have a strong propensity for development of both T2DM and DR. This proposal is a joint effort among three centers: LA Biomed, which is the Clinical Phenotyping Center, the University of Wisconsin, which houses the Ocular Epidemiology Reading Center and Cedars-Sinai Medical Center, where the genetic testing will be done. The clinical center at LA Biomed will target at least 225 large Hispanic families with a mimimum of two, but preferably three diabetic siblings, one of whom has to have DR. Parents and spouses will be encouraged to participate. The families will be ascertained through a family member with DR. Diabetic sibs will undergo phenotyping which will include collection of demographic and clinical data and an eye examination that will include assessment of visual acuity and standard 7-field fundus photographs. Fundus photographs will be read locally for clinically significant findings and graded for research purposes at the Wisconsin Ocular Epidemiology Reading Center, who will also provide expert ophthalmological backup for clinical purposes. We will perform a genome-wide search to identify candidate regions in the genome that may be linked with DR. Non-parametric sib-pair linkage analysis and variance components linkage analysis will be utilized to identify regions that may contain genes contributing to DR. Successful completion of this project is anticipated to result in the initial phase in locating novel gene(s) that confer susceptibility to DR. Characterization of the products of these genes will enhance our understanding of the pathogenesis of DR and has the potential to lead to the development of new preventive and therapeutic strategies. Moreover, availability of genetic markers for DR will allow early identification of patients at risk who should be targeted for intensive glycemic and blood pressure control to prevent DR appearance and/or progression.The risk-benefit ratio is beneficial. There is little risk involved in the procedures, including those of blood drawing, loss of confidentiality, or obtaining eye pictures, although acute angle glaucoma is an extremely rare possibility during dilation of the pupil. There is potential benefit to the patients in whom diabetic eye disease may be diagnosed as well as to patients with T2DM and DR in general due to new information that may be obtained in this proposal.
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