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Original Paper
Ophthalmic Res 2007;39:294–299
DOI: 10.1159/000108124
Diabetic Retinopathy and IGF-1 Gene
Polymorphic Cytosine-Adenine Repeats
in a Southern Indian Cohort
Satagopan Uthra
a
Rajiv Raman
b
Bickol N. Mukesh
d
Samuel A. Rajkumar
a
Padmaja Kumari R.
b
Swati Agarwal
b
Pradeep G. Paul
c
Praveena Lakshmipathy
a
Perumal Gnanamoorthy
c
Tarun Sharma
b
Catherine A. McCarty
d
Govindasamy Kumaramanickavel
a
a
SN ONGC Department of Genetics and Molecular Biology,
b
Shri Baghawan Mahavir Vitreoretinal Services, and
c
Sankara Nethralaya Diabetic Retinopathy Project, Medical and Vision Research Foundations, Sankara Nethralaya,
Chennai, India;
d
Marshfield Clinic Research Foundation, Marshfield, Wisc., USA
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 geno-
type is a susceptibility genotype for DR and its clinical sever-
ity in a Southern Indian cohort.
Copyright © 2007 S. Karger AG, Basel
Introduction
Numerous pathways have been implicated in the
pathogenesis of diabetic retinopathy (DR). Expression of
vascular endothelial growth factor (VEGF) is a crucial
event in the vascular pathology of DR and is known to be
enhanced by various factors during the evolution of reti-
nopathy in a patient who has diabetes. Hypoxia is one of
the most important initiating factors that is responsible
for the activation of transcription factors such as hypox-
ia-inducible factor (HIF)-1 and HIF-1 ; these factors fi-
nally bind to the hypoxia response elements of the VEGF
promoter. Another known modifier of VEGF expression
Key Words
Diabetic retinopathy IGF-1 gene Proliferative diabetic
retinopathy Genetic association studies
Abstract
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 di-
abetic retinal neovascularization. In the present study, a cy-
tosine-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 stereo-
scopic 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 fre-
quency of the 18-repeat genotype was significantly higher
Received: November 6, 2006
Accepted after revision: June 12, 2007
Published online: September 12, 2007
Dr. G. Kumaramanickavel, MD
SN ONGC Department of Genetics and Molecular Biology
Vision Research Foundation, Sankara Nethralaya, 18, College Road
Chennai 600 006 (India)
Tel. +91 44 4227 1807, Fax +91 44 2825 4180, E-Mail gkumarmvel@rediffmail.com
© 2007 S. Karger AG, Basel
0030–3747/07/0395–0294$23.50/0
Accessible online at:
www.karger.com/ore