title: Cigarette smoking, CFH, APOE, ELOVL4, and risk of neovascular age-related macular degeneration.
abstract: OBJECTIVE
  To examine if the genes encoding complement factor H (CFH), apolipoprotein E (APOE), and elongation of very-long-chain fatty acids-like 4 (ELOVL4) confer risk of neovascular age-related macular degeneration (AMD) in an independent or interactive manner when controlling for smoking exposure.
  
  
  METHODS
  We studied 103 unrelated patients with neovascular AMD who each had at least 1 sibling with normal maculae. Smoking histories were obtained. Genotyping was performed by analyzing amplified genomic fragments from CFH, APOE, and ELOVL4 by direct sequencing or by restriction endonuclease digests. Conditional logistic regression analysis was used to build a multifactor model.
  
  
  RESULTS
  For CFH, only the CC genotype carried a statistically significant elevation of disease risk (odds ratio, 49.37; 95% confidence interval, 6.20-393.22; P<.001). No significant association was observed between neovascular AMD and APOE or ELOVL4. No significant interactions were found between smoking and having the CFH or APOE genotype nor were significant interactions found between the CFH, ELOVL4, and APOE genotypes.
  
  
  CONCLUSIONS
  Smoking and having the CFH CC genotype independently increase risk of neovascular AMD. APOE and ELOVL4 genotypes do not seem to modify risk.
  
  
  CONCLUSIONS
  Smoking 10 pack-years or more and having the CFH CC genotype increase one's risk of neovascular AMD 144-fold compared with smoking less than 10 pack-years and having the CT or TT genotype.
authors.affiliation: Department of Ophthalmology, Harvard Medical School, and Massachusetts Eye and Ear Infirmary, Boston, USA. margaret_deangelis@hms.harvard.edu
authors.forename: Margaret M
authors.initials: MM
authors.lastname: DeAngelis
authors.forename: Fei
authors.initials: F
authors.lastname: Ji
authors.forename: Ivana K
authors.initials: IK
authors.lastname: Kim
authors.forename: Scott
authors.initials: S
authors.lastname: Adams
authors.forename: Antonio
authors.initials: A
authors.lastname: Capone
authors.forename: Jurg
authors.initials: J
authors.lastname: Ott
authors.forename: Joan W
authors.initials: JW
authors.lastname: Miller
authors.forename: Thaddeus P
authors.initials: TP
authors.lastname: Dryja
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics*; D020256:Choroidal Neovascularization / Q000453:epidemiology* / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D016001:Confidence Intervals; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D017720:Molecular Epidemiology; D016017:Odds Ratio; D012307:Risk Factors; D035781:Siblings; D012907:Smoking / Q000009:adverse effects*; D011795:Surveys and Questionnaires
chemical_list: D001057:Apolipoproteins E; C493495:CFH protein, human; C418975:ELOVL4 protein, human; D005136:Eye Proteins; D008565:Membrane Proteins; D017242:Complement Factor H