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.

Relation between Polymorphisms G1704T and G82S of RAGE Gene and Diabetic Retinopathy in Japanese Type 2 Diabetic Patients

“…Many genetic studies have been reported on the association with the development of DR. For example, proposed genes are angiotensin-converting enzyme gene (15,16), plasminogen activator inhibitor-1 gene (17,18), tumor necrosis factor gene (19,20), aldose reductase gene (21,22), nitric oxide synthase gene (23,24), vascular endothelial growth factor gene (25,26), transforming growth factor-beta gene (27), methylenetetrahydrofolate reductase gene (28,29), fatty acid binding protein 2 gene (30) and so on. However, the linkage of these gene polymorphisms with DR is still controversial because some specific genotypes of genes are associated with a more rapid course of DR, whereas others do not increase the frequency of DR.…”

Relationship between polymorphisms 804C/A and 252A/G of lymphotoxin-α gene and −308G/A of tumor necrosis factor α gene and diabetic retinopathy in Japanese patients with type 2 diabetes mellitus

“…However, why PDR unlike NPDR affects only a subgroup of patients despite the same glycemic control and diabetes duration remains elusive. In addition to conventional risk factors, many genetic studies [4][5][6][7][8][9][10][11] have suggested the contribution of genetic factors to DR.…”

“…Recently, polymorphism (252A/G in intron 1 and 804C/A in exon 3) of the LTA gene has been identified as a major risk factor for myocardial infarction (MI) in Japanese individuals [22]. Although there have been few reports on the association of tumor necrosis factor allelic polymorphism with DR in Caucasian [6] and Indian populations [7], whether this is true for Japanese is currently unknown. We therefore conducted this study to clarify the relationship between polymorphisms 804C/A in exon 3 and 252A/G in intron 1 of the LTA gene as well as À308G/A TNF-a promoter variant and DR in Japanese patients with T2DM.…”

Association between TNF-β NcoI (A252G) gene polymorphism and type I diabetes mellitus in Turkish population

“…Kontrol ve çalışma grubundaki tüm hastalar 18 yaşın üzerindeydi. Tip 1 DM tanısı ADA kriterlerine göre değerlendirildi [15]. Açlık kan şekeri düzeyinin 126 mg/dL' nin üstünde olan bireyler çalışma-ya dahil edildi.…”