Duration of Non-Insulin-Dependent Diabetes mellitus and the TNF-β NcoI Genotype as Predictive Factors in Proliferative Diabetic Retinopathy

Abstract

The object of the study was to investigate the share of the polymorphisms I/D ACE, endothelin 1 4127G/A and TNF-β NcoI in the susceptibility to proliferative diabetic retinopathy (PDR) in non-insulin-dependent diabetes mellitus (NIDDM). Genotypes were detected by polymerase chain reactions and determined in a set of 246 Caucasian NIDDM subjects with defined PDR status. The relevance of genotypes and clinical characteristics to the PDR occurrence was tested using multiple linear regression models and discrimination analysis. The best predictive value for PDR was given by a combination of two parameters – NIDDM duration and the TNF-β genotype (p < 1·10^–6 and p = 1·10^–2, respectively) with a correct retrograde prediction of 82.6%. A comparison of the TNF-β NcoI allele frequencies revealed no difference between NIDDM and nondiabetic subjects (n = 176), but a statistically significant difference was found between PDR and non-PDR NIDDM subjects (after a correction for the number of comparisons p = 0.03), allele β₂ being associated with PDR. Our results identified the allele variant TNF-β₂ being associated with PDR in NIDDM. Diabetes duration and the TNF-β NcoI genotype were proven to significantly predict PDR occurrence. The TNF-β₂ allele could be regarded as a separate genetic risk factor that increases the relative incidence of PDR in patients with NIDDM.