Genetic risk factors in diabetic retinopathy

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Abstract
Diabetic retinopathy is the leading cause of blindness in adults aged 30 to 65 years. However, 20% of the diabetic population does not develop significant retinopathy. To examine the influence of immune-related genetic factors on the development of diabetic retinopathy, we studied immunoglobulin allotypes in 102 subjects aged 8 to 20 years, who had had Type 1 (insulin-dependent) diabetes mellitus for 4.5 to 11 years (mean 7.3 years). HLA had been previously typed on 59 of these subjects. Retinopathy was assessed by expert review of retinal photographs. Among the 44 patients who had evidence of retinopathy, 33(75%) were G2m(23 +), while among the 58 patients without retinopathy but with similar duration of disease, only 28(48%) were G2m(23 +) (p = 0.006). The HLA-DR types of patients with and without retinopathy were not significantly different. We conclude that there is significant evidence of an association between G2m(23) at the locus encoding IgG2 subclass heavy chains and susceptibility to the development of diabetic retinopathy early in the clinical course of the disease. Our findings provide important independent confirmation of a previous report of association between Gm allotypes and predisposition to diabetic retinopathy. We are unable to determine if the Gm effect on development of retinopathy is due to the G2m(23) allotype itself, or due to genes that are closely linked to, and in linkage disequilibrium with, the locus encoding the G2m(23) allotype.