title: Analysis of variants in the complement factor H, the elongation of very long chain fatty acids-like 4 and the hemicentin 1 genes of age-related macular degeneration in the Finnish population.
abstract: OBJECTIVE
  A strong association of a Tyr402His polymorphism in the complement factor H (CFH) gene and a Met299Val polymorphism in the elongation of very long chain fatty acids-like 4 (ELOVL4) gene with age-related macular degeneration (AMD) has been identified in Caucasian populations in the United States. Earlier a Gln5345Arg variant in the hemicentin 1 (HMCN1) gene was reported in a large AMD family in the United States. We wanted to investigate whether the polymorphisms of the CFH and the ELOVL4 genes or the mutation of the HMCN1 gene are associated with AMD in patients originating from the Finnish population with characteristics of a genetic isolate.
  
  
  METHODS
  The material consisted of familial (n=181) and sporadic cases (n=154) with AMD, a control group with no AMD (non-AMD controls, n=105), and a control group of anonymous blood donors (blood donor controls, n =350). The DNA of the subjects was sequenced to analyze the variants of the three genes.
  
  
  RESULTS
  We detected a strong association between the C/C-genotype compared to the T/T-genotype of Tyr402His polymorphism (first base of the Tyr-codon changes) of the CFH gene and AMD in the AMD cases compared to the non-AMD (p=8.86x10(-12)) or to blood donor controls (p=2.02x10(-13)). The frequency of the C/C genotype was significantly increased in both familial cases compared to non-AMD controls with non-adjusted odds ratio (OR) 10.1 (confidence intervals [CI] 95% 4.64-22.2) or compared to blood donor controls with non-adjusted OR 5.50 (CI 95% 3.17-9.55) and in sporadic cases with non-adjusted OR 9.33 (CI 95% 4.10-21.3; non-AMD-controls), OR 5.06 (CI 95% 2.75-9.28; blood donor controls). Frequency of C allele differed significantly between cases and controls (p=1.32x10(-11); non-AMD-controls and p=3.94x10(-14); blood donor controls). No association with AMD was detected with Met299Val polymorphism in the ELOVL4 gene in the familial or sporadic cases compared to non-AMD or blood donor controls. None of our subjects (258 AMD cases, 72 non-AMD controls) had the Gln5345Arg variant in the HMCN1 gene.
  
  
  CONCLUSIONS
  The CFH gene polymorphism seems to be an important etiologic factor for AMD also in the isolated Finnish population.
authors.affiliation: Department of Ophthalmology, University of Helsinki, Helsinki, Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Seitsonen
authors.forename: Susanna
authors.initials: S
authors.lastname: Lemmelä
authors.forename: Juha
authors.initials: J
authors.lastname: Holopainen
authors.forename: Petri
authors.initials: P
authors.lastname: Tommila
authors.forename: Päivi
authors.initials: P
authors.lastname: Ranta
authors.forename: Antti
authors.initials: A
authors.lastname: Kotamies
authors.forename: Jukka
authors.initials: J
authors.lastname: Moilanen
authors.forename: Tapani
authors.initials: T
authors.lastname: Palosaari
authors.forename: Kai
authors.initials: K
authors.lastname: Kaarniranta
authors.forename: Seppo
authors.initials: S
authors.lastname: Meri
authors.forename: Ilkka
authors.initials: I
authors.lastname: Immonen
authors.forename: Irma
authors.initials: I
authors.lastname: Järvelä
mesh_terms: D000368:Aged; D001782:Blood Donors; D016022:Case-Control Studies; D017242:Complement Factor H / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005387:Finland; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007136:Immunoglobulins; D008268:Macular Degeneration / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*
chemical_list: C418975:ELOVL4 protein, human; D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; C488168:HMCN1 protein, human; D007136:Immunoglobulins; D008565:Membrane Proteins; D017242:Complement Factor H