Single nucleotide polymorphisms in MCP-1 and its receptor are associated with the risk of age related macular degeneration

PLoS One. 2012;7(11):e49905. doi: 10.1371/journal.pone.0049905. Epub 2012 Nov 21.

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.

Methods and findings: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Chemokine CCL2 / genetics*
  • Female
  • Flow Cytometry
  • Genetic Association Studies*
  • Humans
  • Macular Degeneration / genetics*
  • Macular Degeneration / pathology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Receptors, CCR2 / genetics*
  • Risk Factors

Substances

  • CCL2 protein, human
  • CCR2 protein, human
  • Chemokine CCL2
  • Receptors, CCR2

Grants and funding

The funding of study was from Department of Science and Technology(F.No. SR/SO/HS-109/205 dated 1-05-2007). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.