Duration of non-insulin-dependent diabetes mellitus and the TNF-beta Ncol genotype as predictive factors in proliferative diabetic retinopathy

The object of the study was to investigate the share of the polymorphisms I /D ACE, endothelin 1 4127G/A and TNF-beta Ncol in the susceptibility to pro liferative diabetic retinopathy (PDR) in non-insulin-dependent diabetes mel litus (NIDDM). Genotypes were detected by polymerase chain reactions and de termined in a set of 246 Caucasian NIDDM subjects with defined PDR status. The relevance of genotypes and clinical characteristics to the PDR occurren ce was tested using multiple linear regression models and discrimination an alysis, The best predictive value for PDR was given by a combination of two parameters - NIDDM duration and the TNF-beta genotype (p < 1.10(-6) and p = 1.10(-2), respectively) with a correct retrograde prediction of 82.6%. A comparison of the TNF-beta Ncol allele frequencies revealed no difference b etween NIDDM and nondiabetic subjects (n = 176), but a statistically signif icant difference was found between PDR and non-PDR NIDDM subjects (after a correction for the number of comparisons p = 0.03), allele pp being associa ted with PDR. Our results identified the allele variant TNF-beta (2) being associated with PDR in NIDDM. Diabetes duration and the TNF-beta Ncol genot ype were proven to significantly predict PDR occurrence. The TNF-beta (2) a llele could be regarded as a separate genetic risk factor that increases th e relative incidence of PDR in patients with NIDDM. Copyright (C) 2001 S. K arger AG, Basel.