摘要
BACKGROUND Diabetic retinopathy(DR)is a leading cause of vision loss in working-age adults,with prevalence varying by population and reaching~34%in northern India.DR arises from chronic hyperglycemia–driven oxidative stress,inflammation,and microvascular dysfunction.Intercellular adhesion molecule-1(ICAM-1)is central to leukocyte adhesion and retinal vascular injury;circulating ICAM-1 is elevated in patients and experimental models.Genetic variants in ICAM-1,notably c.1405A>G(rs5498)and c.721G>A(rs1799969),have been examined as risk markers for microvascular complications.Yet associations with DR are inconsistent across ethnicities,and robust data from northern India are limited,underscoring the need for population-specific studies.AIM To determine the association of ICAM-1 gene polymorphisms with DR in patients with type 2 diabetes mellitus(T2DM)from northern India.METHODS The present study included 614 participants:302 patients with T2DM and DR and 312 patients with T2DM but without DR.The ICAM-1 polymorphism c.1405A>G(rs5498)was analyzed using PCR-restriction fragment length polymorphism,and analysis of c.721G>A(rs1799969)was done using the amplification-refractory mutation system.Further,approximately 10%of samples were validated for both polymorphisms for the observed genotypes by Sanger sequencing.A metaanalysis incorporating nine studies(1844 DR cases and 1595 controls)was also performed to assess the association of ICAM-1 rs5498 with DR risk.RESULTS The allele frequency and genotype distribution of ICAM-1 c.1405A>G polymorphism in the DR and control groups were not significant(P=0.070 and P=0.120,respectively).The GG genotype revealed a 1.6-fold increased risk of developing retinopathy(odds ratio=1.61,95%confidence interval:1.01-2.58,P=0.044).However,the AG genotype did not show any significant association(P=0.643)between DR cases and controls.With c.721G>A in ICAM-1 the onset and progression of retinopathy was not found to be significantly correlated.The metaanalysis revealed no significant association between rs5498 and DR risk in the overall population or in Asians,but a significant association was observed in Caucasians under the allelic and recessive models.CONCLUSION The ICAM-1 rs5498 GG genotype increased retinopathy risk 1.61-fold in northern Indians.Meta-analysis of nine studies found no Asian association;a Caucasian signal warrants caution given limited subgroups and heterogeneity.
基金
Supported by the Department of Biotechnology,Government of India,No.BT/IN/German/13/VK/2010
the Department of Science and Technology,under the SERC FAST Track scheme for young scientists,No.SR/FT/LS-025/2008.
