Relationship Between Human Leukocyte Antigen Status and Proliferative Diabetic Retinopathy in Patients With Younger-onset Type 1 Diabetes Mellitus TATSUYA MIMURA, MD, HIDEHARU FUNATSU, MD, YASUKO UCHIGATA, MD, SHIGEHIKO KITANO, MD, HIDETAKA NOMA, MD, ERIKA SHIMIZU, MD, YASUHIRO KONNO, MD, SHIRO AMANO, MD, MAKOTO ARAIE, MD, OSAMU YOSHINO, MD, YASUHIKO IWAMOTO, MD, AND SADAO HORI, MD ● PURPOSE: To investigate the relationship between hu- man leukocyte antigen (HLA) status and proliferative diabetic retinopathy (PDR) to assess the genetic basis of PDR in younger type 1 diabetic patients. ● DESIGN: Retrospective, nonrandomized, comparative trial. ● METHODS: Patients who were diagnosed with type 1 diabetes under 30 years of age (range, 13–28) and had a disease duration of more than 10 years were studied. The patients were divided into two groups: 30 patients who had undergone vitreous surgery younger than 40 years old (the PDR group) and 50 patients without retinopathy (the non–DR group). The duration of diabetes and the level of glycemic control were matched between the two groups. The control group consisted of 50 healthy pa- tients. HLA-A, -B, -C, -DR, and -DQ typing of blood samples was done using the standard microcytotoxicity method. ● RESULTS: The frequency of HLA-B62, Cw4, and DQ4 was significantly higher in the PDR group than in the non–DR group (P  .0020, P  .048, and P  .0026, respectively). The Cw4-DR4-DQ4 haplotype frequency was significantly higher in the PDR group than in the control group and the non–DR group (P  .0059). ● CONCLUSIONS: Our results suggests that HLA-B62, Cw4, and DQ4 may be useful for predicting the progno- sis of retinopathy in patients with younger-onset type 1 diabetes. (Am J Ophthalmol 2003;135:844 – 848. © 2003 by Elsevier Inc. All rights reserved.) P ROLIFERATIVE DIABETIC RETINOPATHY (PDR) IS THE main cause of visual disturbance in Japan, so it is important to develop methods to prevent the onset and progression of PDR. In the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), the prevalence of any grade of retinopathy was 99.5% after more than 15 years of diabetes, and 67% of younger-onset patients with diabetes for 35 years had PDR. 1 Chronic hyperglycemia and the duration of diabetes are the most important factors related to retinopathy. 2 However, some patients show progression of retinopathy despite good glycemic control. Also, among younger-onset patients, some individuals do not develop retinopathy despite poor glycemic control, whereas others develop severe retinopathy that is resistant to retinal photocoagulation. These facts suggest that the risk factors for diabetes and retinopathy are not necessar- ily the same and that the development of severe retinopathy may be influenced by genetic factors. Over the past 10 years, many studies have investigated retinopathy from a genetic viewpoint, and some reports have suggested that retinopathy is hereditary, 3 but other authors have found no significant genetic influence on retinopathy. 4,5 Thus, the relationship between retinopathy and hereditary factors is still controversial. Human leukocyte antigen (HLA) status plays a signifi- cant role in immune responses and in immunologic toler- ance. HLA status is a major factor in the onset of type 1 diabetes, 6 –10 and it also seems to have a role in the development and progression of retinopathy. 11–15 How- Accepted for publication Dec 17, 2002. InternetAdvance publication at ajo.com Jan 9, 2003. From the Department of Ophthalmology (T.M., S.A., M.A.), Univer- sity of Tokyo School of Medicine; the Departments of Ophthalmology (T.M., H.F., S.K., E.S., Y.K.) and Internal Medicine (Y.U., H.N., Y.I.), Diabetes Center, Tokyo Women’s Medical University; the Department of Obstetrics and Gynecology (O.Y.), University of Tokyo School of Medicine; and the Department of Ophthalmology (S.H.), Tokyo Wom- en’s Medical University, Tokyo, Japan. Inquiries to Tatsuya Mimura, MD, Department of Ophthalmology, University of Tokyo School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655 Japan; fax: (+81 3-3817-0798; e-mail: mimura@mbg. sphere.ne.jp © 2003 BY ELSEVIER INC.ALL RIGHTS RESERVED. 844 0002-9394/03/$30.00 doi:10.1016/S0002-9394(02)02291-2