CCL2 single nucleotide polymorphism of rs1024611 implicates prominence of inflammatory cascade by univariate modeling in Indian AMD.

Abstract

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. Aim of the study was to examine the association of another variance of CCL2, rs1024611 in pathophysiology of AMD. This 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. 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). 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. Based on these results it is imperative that CCL2 mediated pathology may be associated with AMD.