Neuroscience Research Lab, Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Neurobiology Neurodegeneration & Repair Laboratory, National Eye Institute, NIH, Bethesda, United States of America.
PLoS One. 2018 Apr 17;13(4):e0193423. doi: 10.1371/journal.pone.0193423. eCollection 2018.
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.
通过我们之前的研究，趋化蛋白 CCL2/MCP-1 在年龄相关性黄斑变性（AMD）患者和动物模型中的作用已经得到了广泛的探索。
本研究旨在探讨 CCL2 的另一种变异体 rs1024611 在 AMD 发病机制中的作用。
本研究中发现，该特定 SNP 与各种疾病的炎症过程有关。通过管理标准问卷，共招募了 171 名研究对象，记录了所有人口统计学细节。采用 TaqMan assay 进行 SNP 分析。采用线性单变量和协方差分析模型来显示 rs1024611 与 CCL-2/CCR-2 的另一个 SNP 变异体（rs4586 和 rs1799865）的相互作用以及个体基因型对 AMD 病理条件下 CCL-2 表达的影响。
结果表明，杂合子（AG，p=0.01）和纯合子（GG，p=0.0001）基因型均与 AMD 病理相关。等位基因频率分析表明，与对照组相比，AMD 患者的“G”等位基因更为常见（p=0.0001）。此外，我们发现吸烟的 AMD 患者与“AG”基因型相关（p=0.0145）。虽然线性单变量分析未发现 SNP 变异体之间存在任何显著的相互作用，但结果表明，在考虑 rs1024611 为协变量时，rs4586 中的“CT”基因型对“TT”基因型有影响。
基于这些结果，CCL2 介导的病理学可能与 AMD 相关。
