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Jane Z. Kuo, Xiuqing Guo, Ronald Klein, Barbara E. Klein, Jerome I. Rotter, Eli Ipp, Yii-Der Ida Chen; Systemic Soluble TNF Receptors 1 and 2 are Associated with Severity of Diabetic Retinopathy in Mexican-Americans. Invest. Ophthalmol. Vis. Sci. 2011;52(14):605.
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The purpose of this study was to evaluate the association of the proinflammatory cytokines, tumor necrosis factor-α (TNF-α) soluble receptors TNF-R1 and TNF-R2 with diabetic retinopathy (DR) in a large group of family-based Hispanic diabetic patients. The soluble receptors are surrogate measures of TNF-α and inflammatory states.
Levels of TNF-R1 and TNF-R2 were investigated in the plasma of 501 consecutive type 2 diabetic subjects using specific enzyme-linked immunoabsorbent assays (ELISA). Severity of DR was assessed by fundus photography of 30° ETDRS 7SF and graded using modified Airlie House classification. Statistical comparison of values in various groups was performed using GENMOD in SAS, adjusting for family relationships.
DR was present in 267 (53.3%) subjects, of whom 75 subjects had mild non-proliferative DR (NPDR), 105 had moderate NPDR, 22 had severe NPDR, 62 had proliferative DR (PDR), and 3 had ungradeable fundus photos. We found TNF-R1 (mean ± SEM; 2.32±0.15, 2.15±0.27, 3.09±0.23, 3.25±0.49, 5.02±0.31 ng/ml for No DR, Mild NPDR, Moderate NPDR, Severe NPDR, PDR, respectively; p=0.006) and TNF-R2 (5.91±0.42, 6.23±0.74, 7.97±0.62, 8.14±1.34, 14.83±0.80 ng/ml for No DR, Mild NPDR, Moderate NPDR, Severe NPDR, PDR, respectively; p=0.03) increased with severity of DR after adjustment for age, body mass index, hemoglobin A1c, diabetes duration, systolic blood pressure, and albumin-to-creatinine ratio.
Increased TNF-R1 and TNF-R2 are highly correlated with severity of DR, implicating inflammation in the pathogenesis of DR. These may be effective biomarkers for DR, aiding etiologic studies, and identifying at risk patients for interventions.
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