Short communication CC chemokine receptor-3 as new target for age-related macular degeneration Neel Kamal Sharma a , Amod Gupta b , Sudesh Prabhakar a , Ramandeep Singh b , Arvind Kumar Bhatt c , Akshay Anand a, ⁎ a Department of Neurology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India b Department of Ophthalmology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India c Department of Biotechnology, Himachal Pradesh University, Shimla, India abstract article info Article history: Accepted 6 March 2013 Available online 6 April 2013 Keywords: CCR3 Inflammation Chemokines Single nucleotide polymorphism Population study AMD CC chemokine receptor-3 (CCR3) is involved in angiogenic processes. Recently, CCR3 was accounted to par- ticipate 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 ad- justed 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) poly- morphism 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. © 2013 Elsevier B.V. All rights reserved. 1. Introduction Age-related macular degeneration (AMD) is a primary cause of central vision loss in the aged in industrialized countries (Cook et al., 2008). Symptoms of AMD may appear in one or in both eyes. Early symptoms include metamorphopsia or blurring of central vi- sion. AMD is characterized by the development of drusen in Bruch's membrane, the degeneration of the macular retinal pigment epitheli- um (RPE), geographic atrophy and neovascularization. According to clinical age-related maculopathy grading system, age-related maculopathy grades are: without drusen, several minute drusen and no RPE changes, retinal RPE alteration but no drusen, both small drusen and RPE changes, several large and intermediate-size drusen, RPE detachment, geographic atrophy and choroidal neovascular membrane with disciform scarring (Seddon et al., 2006). It is established that there is a complex participation of environ- mental and genetic factors in the pathogenesis of AMD. In comple- ment system, microglial recruitment, inflammation, DNA repair, and neovascularization activation studies have identified numerous AMD-associated genes (Ding et al., 2009). A lot of the earlier works done on genetic factors impacting AMD have been focused on single nucleotide polymorphisms (SNPs). Al- though extremely significant statistical relations between various single nucleotide polymorphisms and AMD have been discovered, they do not account for the whole genetic aspect of the disease. It is supposed that complement activation resulting from dysfunction of CC chemokines may contribute to inflammation. The infiltration of monocytes is ac- companied by inflammatory chemokines as key mediators. Studies recently indicated that inflammation plays a fundamental role in the development of CNV (Rohrer et al., 2009). Additionally, ge- netic evidence has identified variations in multiple genes (Sharma et al., 2009). Studies had also investigated the role of asthma with AMD and found that asthma could be a risk factor for AMD (Sun et al., 2012). In senescent mice deficient in monocyte chemoattractant protein-1 (CCL2, also known as MCP-1) or its receptor we earlier described the Gene 523 (2013) 106–111 Abbreviations: 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. ⁎ Corresponding author. Tel.: +91 9914209090, +91 1722756094; fax: +91 1722748399. E-mail address: akshay1anand@rediffmail.com (A. Anand).URL: http://www.neurologypgi.org (A. Anand). 0378-1119/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.gene.2013.03.052 Contents lists available at SciVerse ScienceDirect Gene journal homepage: www.elsevier.com/locate/gene