title: Joint effect of cigarette smoking and CFH and LOC387715/HTRA1 polymorphisms on polypoidal choroidal vasculopathy.
abstract: OBJECTIVE
  To investigate whether the major genetic and environmental risk factors of age-related macular degeneration (AMD)-CFH Y402H and LOC387715 A69S and cigarette smoking-are also associated with polypoidal choroidal vasculopathy (PCV) and whether the associations of CFH Y402H and LOC387715 A69S with PCV are modified by smoking.
  
  
  METHODS
  Three hundred seventy-five Japanese patients with PCV and 847 Japanese who served as population-based control subjects, all ≥55 years of age, were studied. CFH Y402H (rs1061170) and LOC387715 A69S (rs10490924) were genotyped with a single-nucleotide polymorphism (SNP) assay. An unconditional logistic regression model was used to analyze the association between age, sex, smoking status, CFH Y402H, LOC387715 A69S, and PCV. The synergy index (SI) was measured to assess gene-smoking and gene-gene interaction as a departure from additivity.
  
  
  RESULTS
  CFH Y402H, LOC3387715 A69S, and cigarette smoking status were all significantly associated with PCV; for CFH Y402H, the adjusted odds ratio (OR) for the number of copies of the allele was 1.63 (95% confidence interval [CI], 1.12-2.36; P < 0.05); for LOC387715 A69S, the adjusted OR was 2.26 (95% CI, 1.83-2.78; P < 0.0001); and for smoking status (ever versus never smoked), the adjusted OR was 1.45 (95% CI, 1.00-2.10; P < 0.05). The joint effect of CFH Y402H and smoking was significantly greater than the additive scale, with an SI of 2.41 (95% CI, 1.14-5.10).
  
  
  CONCLUSIONS
  CFH Y402H and LOC387715 A69S are both significantly associated with PCV. Cigarette smoking is an environmental risk factor for PCV. The findings suggest interactions between CFH 402H and cigarette smoking in PCV.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan. hideon@kuhp.kyoto-u.ac.jp
authors.forename: Hideo
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamashiro
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamada
authors.forename: Norimoto
authors.initials: N
authors.lastname: Gotoh
authors.forename: Hisako
authors.initials: H
authors.lastname: Hayashi
authors.forename: Isao
authors.initials: I
authors.lastname: Nakata
authors.forename: Masaaki
authors.initials: M
authors.lastname: Saito
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Iida
authors.forename: Akio
authors.initials: A
authors.lastname: Oishi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kurimoto
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tajima
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
authors.forename: Nagahisa
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D002829:Choroid / Q000098:blood supply; D015862:Choroid Diseases / Q000235:genetics*; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D005838:Genotype; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016491:Peripheral Vascular Diseases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000235:genetics*; D012907:Smoking / Q000235:genetics*; D011795:Surveys and Questionnaires
chemical_list: C514392:ARMS2 protein, human; C493495:CFH protein, human; D011506:Proteins; D017242:Complement Factor H; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases