Abstract

BackgroundThe role of chemotactic protein CCL2/MCP-1 has been widely explored in age related macular degeneration (AMD) patients as well as animal models through our previous studies.AimAim of the study was to examine the association of another variance of CCL2, rs1024611 in pathophysiology of AMD.MethodsThis particular SNP has been found to be involved in inflammatory processes in various diseases. Total 171 subjects were recruited in the study with all demographic details by administering a standard questionnaire. SNP analysis was performed with TaqMan assay. Linear univariate and ANCOVA modeling was performed to show the interaction of rs1024611 with another SNP variant of CCL-2/CCR-2 (rs4586 and rs1799865) and impact of individual genotypes on CCL-2 expression in the context of AMD pathology.ResultsResults showed that both heterozygous (AG, p = 0.01) and homozygous (GG, p = 0.0001) genotypes are associated with AMD pathology. Allele frequency analysis showed that ‘G’ allele is frequent in AMD patients as compared to controls (p = 0.0001). Moreover, AMD patients who smoke were found to be associated with ‘AG’ genotype (p = 0.0145). Although, we did not find any significant interaction between the SNP variants by linear univariate analysis but results show the effect of ‘CT’ genotype on ‘TT’ genotype in rs4586 by considering rs1024611 as covariate.ConclusionBased on these results it is imperative that CCL2 mediated pathology may be associated with AMD.

Highlights

  • age related macular degeneration (AMD) can be defined with several pathological conditions including drusen formation, macrophages infiltration, apoptosis of retinal cell layers and new blood vessels formation from the choroid

  • Results showed that both heterozygous (AG, p = 0.01) and homozygous (GG, p = 0.0001) genotypes are associated with AMD pathology

  • Allele frequency analysis showed that ‘G’ allele is frequent in AMD patients as compared to controls (p = 0.0001)

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Summary

Introduction

AMD can be defined with several pathological conditions including drusen formation, macrophages infiltration, apoptosis of retinal cell layers and new blood vessels formation from the choroid. The inflammatory processes have been reported in AMD to result in drusen deposits (dry AMD) which can further provoke the wet AMD pathology. These pathological conditions lead to impaired visual function. In case of multivariate analysis the ‘TT’ genotype for both genes i.e. CCL2 (rs4586) and CCR2 (rs1799865) were significantly associated with AMD pathophysiology after adjusting for age (p = 0.005) and gender (p = 0.017) respectively. Elevated expression levels of CCL2 and CCR2 in serum and lymphocytes respectively, in AMD patients, as compared to controls, have indicated the effect of chemokine ligands and receptors mediating cellular inflammatory processes in AMD pathophysiology [4]. The role of chemotactic protein CCL2/MCP-1 has been widely explored in age related macular degeneration (AMD) patients as well as animal models through our previous studies

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