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CC chemokine receptor-3 as new target for age-related macular degeneration
Authors:Neel Kamal Sharma  Amod Gupta  Sudesh Prabhakar  Ramandeep Singh  Arvind Kumar Bhatt  Akshay Anand
Affiliation:1. Department of Neurology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India;2. Department of Ophthalmology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India;3. Department of Biotechnology, Himachal Pradesh University, Shimla, India
Abstract:CC chemokine receptor-3 (CCR3) is involved in angiogenic processes. Recently, CCR3 was accounted to participate in choroidal neovascularization (CNV) and CCR3 targeting was reported to be superior to standard antivascular endothelial growth factor-A (VEGF-A) administration when tested in an artificially induced CNV in animals. As human CCR3 studies are lacking in age-related macular degeneration (AMD) patients we sought to determine if CCR3 has any association with inflammatory processes that occur in CNV. A total of 176 subjects were included on the basis of inclusion criteria. Real time PCR was used to analyze the single nucleotide polymorphism in CCR3 of AMD (115) and normal controls (n = 61). Genotype frequency was adjusted for possible confounders like cigarette smoking, alcohol, meat consumption and other risk factors. Chi-square test was used for analysis of polymorphism. The genotype distribution of CCR3 (rs3091250) polymorphism was significantly different in AMD patients in the Indian population. GT (heterozygous) and TT (homozygous) at the rs3091250 SNP increased risk of AMD as compared to the GG genotypes (OR = 4.8, CI 95% = 2.2–10.8 and OR = 4.1, CI 95% = 1.6–10.1 respectively). Subgroup analysis of AMD patients in wet and dry revealed no significant differences. There was no significant difference for rs3091312 in AMD and control group. A significant association between AMD and CCR3 (rs3091250) polymorphism localized on chromosome 3p21.3 was detected. The results suggest the possible contribution of rs3091250, a new predisposing allele in AMD.
Keywords:AMD, age-related macular degeneration   CCR3, CC chemokine receptor-3   CEC, choroidal endothelial cell   CNV, choroidal neovascularization   FFA, fluorescein fundus angiography   GPCR, G-protein-coupled receptor   MCP1, monocyte chemoattractant protein-1   OCT, optical coherence tomography   RPE, retinal pigment epithelium   SDS, Sequence Detection System   SNPs, single nucleotide polymorphisms   VEGF-A, vascular endothelial growth factor-A
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