title: Association of combined cigarette smoking and ARMS2/LOC387715 A69S polymorphisms with age-related macular degeneration: A meta-analysis.
abstract: The age-related maculopathy susceptibility2 (ARMS2)/LOC387715 A69S (rs10490924) polymorphism and cigarette smoking have been shown to have significant association with AMD. In this meta-analysis we used the results of available association studies of combined ARMS2/LOC387715 genotypes and cigarette smoking with AMD to estimate the possible synergistic or multiplicative effects.
  
  
  
  Heterogeneity of studies was evaluated using the Cochran Q-test and the I-square index. To compensate for the heterogeneity of the variables in the study we used a random effects model. Meta-analysis was performed using STATA. To estimate the additive or supra-additive effects, we calculated relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), synergy index (S), and multiplicative index (V).
  
  
  
  We could include four studies with 1982 AMD patients and 1797 control subjects. Considering the GG-no smoking as a reference line the meta-analysis result of AMD odds ratios for stratified combined factors was 3.05 (95% CI 2.32-4.02) for nonGG-no smoking, 2.24 (95% CI 1.39-3.63) for GG-smoking and 4.59 (95% CI 3.51-6.01) for nonGG-smoking. The meta-analysis of synergy analysis revealed RERI = 2.01 (95% CI 1.01-3.25), AP = 0.40 (95% CI 0.22-0.54), S = 2.02 (95% CI 1.35-3.01), and V = 1.31 (95% CI 0.94-1.83).
  
  
  
  This analysis revealed the synergistic effect of these two factors indicating that there is a common pathway of ARMS2/LOC387715 and smoking in AMD pathogenesis which may be the complement system pathway.
authors.affiliation: a 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: b Department of Biostatistics and Epidemiology , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Yaseri
authors.affiliation: c Center of Excellence for Biodiversity, Faculty of Natural Sciences , University of Tabriz , Tabriz , Iran.
authors.forename: Mortaza
authors.initials: M
authors.lastname: Bonyadi
authors.affiliation: a 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
authors.affiliation: a Ocular Tissue Engineering Research Center, Ophthalmic Research Center , Shahid Beheshti University of Medical Sciences , Tehran , Iran.
authors.forename: Homayoun
authors.initials: H
authors.lastname: Nikkhah
mesh_terms: D000483:Alleles; D000073865:Cigarette Smoking / Q000235:genetics*; D017242:Complement Factor H / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*
chemical_list: C514392:ARMS2 protein, human; D011506:Proteins; D017242:Complement Factor H
keywords: ARMS2/LOC387715 A69S; Age-related macular degeneration (AMD); cigarette smoking; mechanism of pathogenesis; meta-analysis; rs10490924; synergistic effect