It has been suggested that HLA-DR4 is a marker of genetic predisposition to proliferative retinopathy. To investigate this relationship and potential associations between other polymorphic genes and proliferative retinopathy, a sample (n = 428) of participants in the population-based Wisconsin Epidemiologic Study of Diabetic Retinopathy was selected for typing for HLA-A, -B, -C, and -DR and a panel of other polymorphic genes. The presence of proliferative retinopathy was determined from grading of stereoscopic color fundus photographs taken at 2 examinations, 4 yr apart. In logistic regression models with repeated measures, persons with HLA-DR4 who were negative for DR3 were five times more likely to have proliferative retinopathy than those negative for both antigens after adjusting for other potential risk factors (Odds ratio = 5.43, 95% Confidence Interval (Cl) = 1.04, 28.30). HLA-C2, AK-2, and MNSs-S also were associated positively with proliferative retinopathy, and HLA-DR8 was associated inversely with this complication of diabetes in each case before adjusting for the number of comparisons. These data suggest that the genetically determined immunopathic mechanisms leading to diabetes, and in linkage disequilibrium with DR4, may independently contribute to the development of proliferative retinopathy.
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Original Articles|
July 01 1992
Genetic Marker Associations With Proliferative Retinopathy in Persons Diagnosed With Diabetes Before 30 yr of age
Karen J Cruickshanks;
Karen J Cruickshanks
University of Wisconsin Department of Ophthalmology
Madison, Wisconsin
Cedars-Sinai and UCLA School of Medicine, Departments of Medicine and Pediatrics, Division of Medical Genetics
Los Angeles, California
UCLA Center for Health Sciences, Division of Medical Genetics
Los Angeles, California
Immunologic et Immunogenetique Humaine
INSERM U100, Toulouse, France
University of Florida, Department of Pathology and Laboratory Medicine
Gainesville, Florida
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Constance M Vadheim;
Constance M Vadheim
University of Wisconsin Department of Ophthalmology
Madison, Wisconsin
Cedars-Sinai and UCLA School of Medicine, Departments of Medicine and Pediatrics, Division of Medical Genetics
Los Angeles, California
UCLA Center for Health Sciences, Division of Medical Genetics
Los Angeles, California
Immunologic et Immunogenetique Humaine
INSERM U100, Toulouse, France
University of Florida, Department of Pathology and Laboratory Medicine
Gainesville, Florida
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Scot E Moss;
Scot E Moss
University of Wisconsin Department of Ophthalmology
Madison, Wisconsin
Cedars-Sinai and UCLA School of Medicine, Departments of Medicine and Pediatrics, Division of Medical Genetics
Los Angeles, California
UCLA Center for Health Sciences, Division of Medical Genetics
Los Angeles, California
Immunologic et Immunogenetique Humaine
INSERM U100, Toulouse, France
University of Florida, Department of Pathology and Laboratory Medicine
Gainesville, Florida
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M -P Roth;
M -P Roth
University of Wisconsin Department of Ophthalmology
Madison, Wisconsin
Cedars-Sinai and UCLA School of Medicine, Departments of Medicine and Pediatrics, Division of Medical Genetics
Los Angeles, California
UCLA Center for Health Sciences, Division of Medical Genetics
Los Angeles, California
Immunologic et Immunogenetique Humaine
INSERM U100, Toulouse, France
University of Florida, Department of Pathology and Laboratory Medicine
Gainesville, Florida
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William J Riley;
William J Riley
University of Wisconsin Department of Ophthalmology
Madison, Wisconsin
Cedars-Sinai and UCLA School of Medicine, Departments of Medicine and Pediatrics, Division of Medical Genetics
Los Angeles, California
UCLA Center for Health Sciences, Division of Medical Genetics
Los Angeles, California
Immunologic et Immunogenetique Humaine
INSERM U100, Toulouse, France
University of Florida, Department of Pathology and Laboratory Medicine
Gainesville, Florida
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Noel K MacLaren;
Noel K MacLaren
University of Wisconsin Department of Ophthalmology
Madison, Wisconsin
Cedars-Sinai and UCLA School of Medicine, Departments of Medicine and Pediatrics, Division of Medical Genetics
Los Angeles, California
UCLA Center for Health Sciences, Division of Medical Genetics
Los Angeles, California
Immunologic et Immunogenetique Humaine
INSERM U100, Toulouse, France
University of Florida, Department of Pathology and Laboratory Medicine
Gainesville, Florida
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Deston Langfield;
Deston Langfield
University of Wisconsin Department of Ophthalmology
Madison, Wisconsin
Cedars-Sinai and UCLA School of Medicine, Departments of Medicine and Pediatrics, Division of Medical Genetics
Los Angeles, California
UCLA Center for Health Sciences, Division of Medical Genetics
Los Angeles, California
Immunologic et Immunogenetique Humaine
INSERM U100, Toulouse, France
University of Florida, Department of Pathology and Laboratory Medicine
Gainesville, Florida
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Robert S Sparkes;
Robert S Sparkes
University of Wisconsin Department of Ophthalmology
Madison, Wisconsin
Cedars-Sinai and UCLA School of Medicine, Departments of Medicine and Pediatrics, Division of Medical Genetics
Los Angeles, California
UCLA Center for Health Sciences, Division of Medical Genetics
Los Angeles, California
Immunologic et Immunogenetique Humaine
INSERM U100, Toulouse, France
University of Florida, Department of Pathology and Laboratory Medicine
Gainesville, Florida
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Ronald Klein;
Ronald Klein
University of Wisconsin Department of Ophthalmology
Madison, Wisconsin
Cedars-Sinai and UCLA School of Medicine, Departments of Medicine and Pediatrics, Division of Medical Genetics
Los Angeles, California
UCLA Center for Health Sciences, Division of Medical Genetics
Los Angeles, California
Immunologic et Immunogenetique Humaine
INSERM U100, Toulouse, France
University of Florida, Department of Pathology and Laboratory Medicine
Gainesville, Florida
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Jerome I Rotter
Jerome I Rotter
University of Wisconsin Department of Ophthalmology
Madison, Wisconsin
Cedars-Sinai and UCLA School of Medicine, Departments of Medicine and Pediatrics, Division of Medical Genetics
Los Angeles, California
UCLA Center for Health Sciences, Division of Medical Genetics
Los Angeles, California
Immunologic et Immunogenetique Humaine
INSERM U100, Toulouse, France
University of Florida, Department of Pathology and Laboratory Medicine
Gainesville, Florida
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Address correspondence and reprint requests to Karen J. Cruickshanks, PhD, Dept. of Ophthalmology, University of Wisconsin, 610 North Walnut Street, WARF 403, Madison, Wl 53705–2397.
Diabetes 1992;41(7):879–885
Article history
Received:
November 12 1991
Revision Received:
February 20 1992
Accepted:
February 20 1992
PubMed:
1612203
Citation
Karen J Cruickshanks, Constance M Vadheim, Scot E Moss, M -P Roth, William J Riley, Noel K MacLaren, Deston Langfield, Robert S Sparkes, Ronald Klein, Jerome I Rotter; Genetic Marker Associations With Proliferative Retinopathy in Persons Diagnosed With Diabetes Before 30 yr of age. Diabetes 1 July 1992; 41 (7): 879–885. https://doi.org/10.2337/diab.41.7.879
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