title: The genetic variant rs4073 A→T of the Interleukin-8 promoter region is associated with the earlier onset of exudative age-related macular degeneration.
abstract: OBJECTIVE
  To study the association of the single nucleotide polymorphism (SNP) rs4073 in the interleukin-8 (IL-8) promoter region with the diagnosis and age of onset of exudative age-related macular degeneration (AMD) in association with the known genetic risk factors for AMD and tobacco smoking.
  
  
  METHODS
  Medical records, smoking history and angiograms or fundus photographs of 301 patients with exudative AMD, 72 patients with dry AMD and 119 control subjects were analysed retrospectively. The associations of IL-8 rs4073 A→T, CFH rs1061170 T→C, ARMS2 rs10490924 G→T and C3 rs2230199 C→G SNPs with the presence of AMD and with the age of onset of exudative AMD were analysed.
  
  
  RESULTS
  Younger age of exudative AMD onset was associated with the homozygous AA genotype of IL-8 rs4073 (p = 0.009, Mann-Whitney U-test), CC genotype of CFH rs1061170 (p = 0.016), TT genotype of ARMS2 rs10490924 (p = 0.001) and with current smoking (p = 0.002). The risk alleles C in CFH rs1061170 (p < 0.0001, Pearson chi-square) and T in ARMS2 rs10490924 (p < 0.0001), as well as smoking (p < 0.0001), were more prevalent in AMD patients compared with controls. No association was found between the IL-8 rs4073 genotype and the presence of AMD.
  
  
  CONCLUSIONS
  Out of the factors associated with the earlier onset of exudative AMD, only the genotype of IL-8 rs4073 did not appear as a risk factor for AMD in general. IL-8 may have a role in accelerating the development of the choroidal neovascularization in exudative AMD.
authors.affiliation: Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Asta
authors.initials: A
authors.lastname: Hautamäki
authors.affiliation: Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Seitsonen
authors.affiliation: Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Juha M
authors.initials: JM
authors.lastname: Holopainen
authors.affiliation: Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Jukka A
authors.initials: JA
authors.lastname: Moilanen
authors.affiliation: Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
authors.forename: Jarno
authors.initials: J
authors.lastname: Kivioja
authors.affiliation: Department of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Onkamo
authors.affiliation: Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
authors.forename: Irma
authors.initials: I
authors.lastname: Järvelä
authors.affiliation: Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Immonen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003176:Complement C3 / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D005838:Genotype; D057092:Geographic Atrophy / Q000235:genetics; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000235:genetics; D057135:Wet Macular Degeneration / Q000235:genetics*
chemical_list: C493495:CFH protein, human; C508606:CXCL8 protein, human; D003176:Complement C3; D016209:Interleukin-8; D017242:Complement Factor H
keywords: exudative age-related macular degeneration; genetic associations; interleukin-8; single nucleotide polymorphism