title: Joint association of complement component 3 and CC-cytokine ligand2 (CCL2) or complement component 3 and CFH polymorphisms in age-related macular degeneration.
abstract: To determine the joint effect of complement component 3(C3 R102G) with CC-cytokine ligand2 (CCL2-2518) or complement factor H (CFH) Y402H polymorphisms on advanced age-related macular degeneration (AMD).
  
  
  
  In this case-control study, 233 patients with advanced AMD and 159 unrelated healthy controls enrolled for evaluation. Selected polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism.
  
  
  
  A combination of AA CCL2 (rs1024611) and GG C3 (R102G) genotypes resulted in a super-additivity of the risks: OR = 10.13, 95% CI 1.04-98.49, p = 0.04, adjusted OR = 7.74, 95% CI 0.71-84.75, p < 0.1, adjusted synergy indices: relative excess risk due to interaction (RERI) = 1.38, the attributable proportion due to interaction (AP) = 24.7% and the synergy index (S) = 1.43. Combination of at-risk genotypes of CFH Y402H and C3 R102G resulted in a strong super-additive risk: adjusted OR = 22.65, 95% CI 2.32-220.91, p = 0.007, adjusted AP = 90.4% and the S = 12.86. Attributable proportion of risk owing to C3-CCL2 and C3-CFH interaction calculated at 25% and 90% for advanced AMD.
  
  
  
  We have previously shown a strong association of C3 (R102G) and CFH Y402H with AMD whereas no association was found for CCL2-2518. This study enclosed strong synergistic association of risk genotypes of C3 and CFH Y402H with AMD. We also revealed synergistic influence of CCL2-2518 and the at-risk genotype of the C3 in AMD with an estimated AP = 50.9% (adjusted AP = 24.7%). Present findings show that CCL2-2518 polymorphism is not an innocent bystander in AMD susceptibility when combined with the at-risk genotype of C3 (R102G).
authors.affiliation: a Center of Excellence for Biodiversity, Faculty of Natural Sciences , University of Tabriz , Tabriz , Iran.|b Liver and Gastrointestinal Disease Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Mortaza
authors.initials: M
authors.lastname: Bonyadi
authors.affiliation: c Ocular Tissue Engineering Research Center, Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences , Tehran , Iran.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Jabbarpoor Bonyadi
authors.affiliation: d Department of Biostatistics and Epidemiology , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Yaseri
authors.affiliation: a Center of Excellence for Biodiversity, Faculty of Natural Sciences , University of Tabriz , Tabriz , Iran.
authors.forename: Tahereh
authors.initials: T
authors.lastname: Mohammadian
authors.affiliation: a Center of Excellence for Biodiversity, Faculty of Natural Sciences , University of Tabriz , Tabriz , Iran.
authors.forename: Nikou
authors.initials: N
authors.lastname: Fotouhi
authors.affiliation: e Department of Ophthalmology , Tabriz University of Medical Sciences , Tabriz , Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Javadzadeh
authors.affiliation: c Ocular Tissue Engineering Research Center, Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences , Tehran , Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Soheilian
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics*; D003176:Complement C3 / Q000235:genetics*; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide
chemical_list: C111835:CCL2 protein, human; C493495:CFH protein, human; D018932:Chemokine CCL2; D003176:Complement C3; D017242:Complement Factor H
keywords: Age-related macular degeneration (AMD); C3 rs2230199 (R102G); CCL2-2518 (rs1024611); CFH Y402H rs1061170; genetic polymorphism; synergistic association