title: Single nucleotide polymorphisms in MCP-1 and its receptor are associated with the risk of age related macular degeneration.
abstract: BACKGROUND
  Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population. We have shown previously that mice deficient in monocyte chemoattractant protein-1 (MCP1/CCL2) or its receptor (CCR2) develop the features of AMD in senescent mice, however, the human genetic evidence so far is contradictory. We hypothesized that any dysfunction in the CCL2 and its receptor result could be the contributing factor in pathogenesis of AMD.
  
  
  RESULTS
  133 AMD patients and 80 healthy controls were enrolled for this study. Single neucleotid Polymorphism for CCL2 and CCR2 was analyzed by real time PCR. CCL2 levels were determined by enzyme-linked immunosorbent assay (ELISA) after normalization to total serum protein and percentage (%) of CCR2 expressing peripheral blood mononuclear cells (PBMCs) was evaluated using Flow Cytometry. The genotype and allele frequency for both CCL2 and CCR2 was found to be significantly different between AMD and normal controls. The CCL2 ELISA levels were significantly higher in AMD patients and flow Cytometry analysis revealed significantly reduced CCR2 expressing PBMCs in AMD patients as compared to normal controls.
  
  
  CONCLUSIONS
  We analyzed the association between single neucleotide polymorphisms (SNPs) of CCL2 (rs4586) and CCR2 (rs1799865) with their respective protein levels. Our results revealed that individuals possessing both SNPs are at a higher risk of development of AMD.
authors.affiliation: Department of Neurology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. akshay1anand@rediffmail.com
authors.forename: Akshay
authors.initials: A
authors.lastname: Anand
authors.forename: Neel Kamal
authors.initials: NK
authors.lastname: Sharma
authors.forename: Amod
authors.initials: A
authors.lastname: Gupta
authors.forename: Sudesh
authors.initials: S
authors.lastname: Prabhakar
authors.forename: Suresh Kumar
authors.initials: SK
authors.lastname: Sharma
authors.forename: Ramandeep
authors.initials: R
authors.lastname: Singh
authors.forename: Pawan Kumar
authors.initials: PK
authors.lastname: Gupta
mesh_terms: D000368:Aged; D018932:Chemokine CCL2 / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D056726:Genetic Association Studies; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054390:Receptors, CCR2 / Q000235:genetics*; D012307:Risk Factors
chemical_list: C111835:CCL2 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D054390:Receptors, CCR2