Rage gene promoter polymorphisms and diabetic retinopathy in a clinic-based population from South India

• Published in: Eye (London) Vol. 21; no. 3; pp. 395 - 401
• Main Authors: RAMPRASAD, S, RADHA, V, MATHIAS, R. A, MAJUMDER, P. P, RAO, M. R. S, REMA, M
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01-03-2007
• Subjects: Biological and medical sciences; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; Diabetic Retinopathy - blood; Diabetic Retinopathy - epidemiology; Diabetic Retinopathy - genetics; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Gene Deletion; Gene Frequency - genetics; Haplotypes; Humans; India - epidemiology; Male; Medical sciences; Middle Aged; Miscellaneous; Ophthalmology; Phenotype; Polymorphism, Genetic - genetics; Polymorphism, Single Nucleotide - genetics; Promoter Regions, Genetic - genetics; Receptor for Advanced Glycation End Products; Receptors, Immunologic - genetics; Retinopathies; Asia; India; Endocrinopathy; Retinopathy; 429 TC; Diabetes mellitus; diabetic retinopathy; Promoter; Eye disease; 63 bp deletion; Gene; Deletion; RAGE polymorphism; Ophthalmology; 374 TA; Polymorphism
• ISSN: 0950-222X; 1476-5454
• DOI: 10.1038/sj.eye.6702239

The main objective of this study was to evaluate if the -429T/C, -374T/A and 63 bp deletion polymorphisms in the RAGE gene are associated with diabetic retinopathy (DR) among Type 2 diabetic subjects in a clinic-based population from South India.
We screened 149 normal glucose tolerant subjects (NGT), 189 Type 2 diabetes subjects without retinopathy (DM) and 190 subjects with DR for these polymorphisms using the PCR-RFLP method. DR was diagnosed by grading color fundus photography. Logistic regression models were used to evaluate the association of individual polymorphisms with DR. Expectation-maximization algorithms were implemented in haplotype tests of association to examine the combined effects of -429T/C and -374T/A polymorphisms on DR.
The allelic frequencies of -429T are 0.83 in NGT, 0.84 in DM and 0.85 in DR subjects, and that of -374T are 0.93 in NGT, 0.92 in DM and 0.88 in DR subjects. The -374 polymorphism was found to be associated with non-proliferative retinopathy when this subgroup was compared to the DM group (OR=1.814, 95% CI=1.005-3.273). However, this association was not obvious when both the subphenotypes of DR (the nonproliferative and proliferative DR groups) were studied jointly. We found no evidence for associations between the -429T/C polymorphism and the DR phenotype. Finally, extension to a 2-SNP haplotype did not reveal any significant statistical difference between the groups (P=0.668).
In this study, we found a modest association with the -374T/A polymorphism in the nonproliferative DR subgroup.