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


METHODS
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.


RESULTS
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).


CONCLUSIONS
In this study, we found a modest association with the -374T/A polymorphism in the nonproliferative DR subgroup.
Ramprasad
S
S
Madras Diabetes Research Foundation & Dr Mohan's Diabetes Specialities Centre Gopalapuram, Chennai, India.
Radha
V
V
Mathias
R A
RA
Majumder
P P
PP
Rao
M R S
MR
Rema
M
M
D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics*
D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic