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


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-β, genes were associated with susceptibility to DR. Gly82Ser polymorphisms of the RAGE gene were not associated with DR in the present study.


CONCLUSIONS
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.
SN ONGC Department of Genetics and Molecular Biology, Medical and Vision Research Foundations, Sankara Nethralaya, Chennai, India. uthrab2306@gmail.com
Satagopan
S
Uthra
Rajiv
R
Raman
Bickol N
BN
Mukesh
Samuel A
SA
Rajkumar
Padmaja
P
Kumari
Praveena
P
Lakshmipathy
Perumal
P
Gnanamoorthy
Tarun
T
Sharma
Catherine A
CA
McCarty
Govindasamy
G
Kumaramanickavel
D000368:Aged; D000449:Aldehyde Reductase / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D003930:Diabetic Retinopathy / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007194:India; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics*
D017931:DNA Primers; D008233:Lymphotoxin-alpha; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C484670:AKR1B1 protein, human; D000449:Aldehyde Reductase; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II