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Luís F. C. Sesti, Daisy Crispim, Luís H. Canani, Evelise R. Polina, Jakeline Rheinheimer, Patrícia S. Carvalho, Jorge L. Gross, Kátia G. Santos; The −308G>A Polymorphism of the TNF Gene Is Associated With Proliferative Diabetic Retinopathy in Caucasian Brazilians With Type 2 Diabetes. Invest. Ophthalmol. Vis. Sci. 2015;56(2):1184-1190. doi: 10.1167/iovs.14-15758.
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© ARVO (1962-2015); The Authors (2016-present)
We tested the hypothesis that tumor necrosis factor (TNF) gene polymorphisms are associated with diabetic retinopathy (DR) in Caucasians with type 2 diabetes mellitus.
In a case-control study, the −238G>A (rs361525), −308G>A (rs1800629), and −857C>T (rs1799724) polymorphisms of the TNF gene were genotyped in 745 outpatients with type 2 diabetes, including 331 subjects without DR, 246 with nonproliferative DR (NPDR), and 168 with proliferative DR (PDR).
Genotype and allele frequencies of the −238G>A, −308G>A, and −857C>T polymorphisms in subjects with NPDR were not significantly different from those of subjects without DR (P > 0.05 for all comparisons). However, the A allele of the −308G>A polymorphism was more frequent in subjects with PDR than in those with no DR (18.1% vs. 11.5%, corrected P = 0.035). Multivariate logistic regression analysis showed that the −308A allele was independently associated with an increased risk of PDR, under a dominant model (adjusted odds ratio [aOR], 1.82; 95% confidence interval [CI], 1.11–2.98). The combined analysis of the three polymorphisms also showed that haplotypes containing the −308A allele were associated with an increased risk of PDR (aOR, 2.36; 95% CI, 1.29–4.32).
This study detected, for the first time to our knowledge, an independent association of the −308G>A polymorphism in the TNF gene with PDR in Caucasian Brazilians with type 2 diabetes. This finding suggests that TNF is a potential susceptibility gene for PDR.
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