Diabetic retinopathy and IGF-1 gene polymorphic cytosine-adenine repeats in a Southern Indian cohort.

BACKGROUND/AIMS: Growth factors have been implicated in the pathogenesis of diabetic retinopathy (DR). IGF-1 is known to trigger a critical cascade of molecular events that initiate retinal angiogenesis. Increased vitreous IGF-1 levels have been correlated with the severity of ischemia-associated diabetic retinal neovascularization. In the present study, a cytosine-adenine (CA)(n) repeat in the promoter of the IGF-1 gene is studied for association with DR. METHODS: A total of 127 patients with retinopathy (cases: DR+) and 81 patients without retinopathy (controls: DR-) who had type 2 diabetes were recruited for the study. Patients underwent detailed clinical examination and DR was graded based on stereoscopic digital fundus photographs. Frequencies of alleles and genotypes between the two groups were analyzed for significance using relevant statistical tests. (CA)(17) and (CA)(18) repeats were the more frequent alleles. RESULTS: The frequency of the 18-repeat genotype was significantly higher in DR+ patients when compared to DR- patients and found to confer a 2.4 times (95% CI: 1.2-5.0) and 2.8 times (95% CI: 1.1-7.5) higher risk for developing DR and proliferative DR, respectively, when compared to <18-repeat genotypes. CONCLUSIONS: Our study suggests that the 18-repeat genotype is a susceptibility genotype for DR and its clinical severity in a Southern Indian cohort.

Diabetic retinopathy: Validation study of ALR2, RAGE, iNOS and TNFB gene variants in a south Indian cohort.

PURPOSE: We previously reported the association of the Z-2 allele of the promoter dinucleotide repeat in the Aldose reductase (ALR2) gene, the (CCTTT)15 allele in the promoter of inductible nitric oxide synthase (iNOS) gene, and the (GT)13 promoter polymorphism in the tumor necrosis factor ß (TNFB) gene with an increased risk for diabetic retinopathy (DR), and the Gly82Ser polymorphism in the receptor for advanced glycation end products (RAGE) gene and the (GT)9 allele of the TNFB gene with low-risk for DR in a hospital-based self-reported type 2 diabetes mellitus (T2DM) patients. We have repeated the study in a population-based south Indian cohort to validate the same variations in these genes. MATERIALS AND METHODS: Type 2 diabetic patients with and without retinopathy (DR+ and DR- respectively) were recruited. (CA)(n) repeat, Gly82Ser, (CCTTT)(n) repeat and (GT)(n) repeat in ALR2, RAGE, iNOS and TNFB genes respectively were genotyped and their frequencies were analyzed using the relevant statistical tests. RESULTS: Different allelic associations were observed in the present study as compared to our previous reports. Z+2 allele of ALR2, 13-repeat genotype of iNOS, 15-repeat genotype of TNF-ß, genes were associated with susceptibility to DR. Gly82Ser polymorphisms of the RAGE gene were not associated with DR in the present study. CONCLUSION: The present data show a difference in the association of variations in ALR2, iNOS and TNFB genes with DR, when compared to our previous reports; this could be attributed to differences between the study populations of the past and present report.

Protein kinase C beta (PRKCB1) and pigment epithelium derived factor (PEDF) gene polymorphisms and diabetic retinopathy in a south Indian cohort.

PURPOSE: Polymorphisms in protein kinase C beta (PRKCB1) and pigment epithelium derived factor (PEDF) genes have been associated with diabetic nephropathy and retinopathy respectively. Association of promoter polymorphisms-1504C/T and-1440G/T in PRKCB1 gene and sequence variations in exon 4 of PEDF gene are studied with diabetic retinopathy (DR) in a south Indian population based cohort. METHODS: Type 2 diabetic patients with and without retinopathy (DR+ and DR- respectively) were recruited. The promoter region of PRKCB1 gene and exon 4 of PEDF genes were sequenced by polymerase chain reaction based direct sequencing and their frequencies were analyzed using relevant statistical tests. RESULTS: The genotype and alleles of the two promoter polymorphisms of PRKCB1 gene were uniformly distributed among DR+ and DR- and hence were not associated with the disease. The haplotypes were also not significantly associated with DR. A T130T polymorphism observed in the PEDF gene showed modest association with absence of diabetic retinopathy. CONCLUSION: Our results suggest lack of association of PRKCB1 gene promoter polymorphisms and moderate protective association of PEDF gene polymorphism with DR in the south Indian population.

Association of VEGF gene polymorphisms with diabetic retinopathy in a south Indian cohort.

BACKGROUND: Polymorphisms in vascular endothelial growth factor (VEGF) gene have been associated with diabetic retinopathy (DR) in various populations. A promoter polymorphism and a 3'UTR variation are studied for association with DR. MATERIALS AND METHODS: Type 2 diabetic patients with and without retinopathy were recruited. The -634C/G and 936C/T polymorphisms were genotyped by direct sequencing and their frequencies were analyzed using relevant statistical tests. RESULTS: No significant association was observed between genotypes, alleles and haplotypes of -634C/G and 936C/T polymorphisms and DR or its severity. However, C(-634)G genotype was found to increase the risk for DR in patients with microalbuminuria (OR: 8.9, 95% CI: 1.4, 58.3). CONCLUSION: Our study broadly suggests lack of association of VEGF gene polymorphisms with DR.