title: Coding and noncoding variants in the CFH gene and cigarette smoking influence the risk of age-related macular degeneration in a Japanese population.
abstract: OBJECTIVE
  Ethnic variation has been reported in age-related macular degeneration (AMD)-associated Y402H polymorphism in complement factor H (CFH). This variation is evident in the Japanese population. Recently a strong association between a novel single-nucleotide polymorphism (SNP; rs1410996) in the CFH gene and AMD has been identified in Caucasian patients. The present study was undertaken to investigate whether four coding and noncoding variants of the CFH gene, including rs1410996, are associated with AMD in native, unrelated Japanese patients.
  
  
  METHODS
  A total of 188 patients with AMD and 139 control subjects without AMD were recruited for the study. Four SNPs (rs800292, rs1061170, rs1410996, and rs2274700) in the CFH gene were assessed by genotyping assay. The information regarding systemic conditions and lifestyle including smoking were documented in each subject by standardized questionnaire.
  
  
  RESULTS
  The intronic SNP (rs1410996) and the synonymous SNP (rs2274700) were associated with a significant risk of AMD (P = 2.37 x 10(-5) and 3.52 x 10(-5), respectively). A significant association was also noted between a coding variant (rs800292, I62V) and AMD (P = 8.63 x 10(-6)). In contrast, the Y402H variant showed no significant association with AMD (P = 0.101). Two common haplotypes also demonstrated significant association with AMD (P = 1.08 x 10(-3) and 2.00 x 10(-5)). Among the environmental factors, smoking alone had a significant association with AMD (P = 1.17 x 10(-4)).
  
  
  CONCLUSIONS
  Although the Y402H variant was not significantly associated with AMD, other coding and noncoding variants in the CFH gene including rs1410996 and smoking moderately influenced the risk of AMD in a Japanese population.
authors.affiliation: Department of Ophthalmology, Saitama Medical School, Moroyama, Iruma, Saitama, Japan. keisuke@saitama-med.ac.jp
authors.forename: Keisuke
authors.initials: K
authors.lastname: Mori
authors.forename: Peter L
authors.initials: PL
authors.lastname: Gehlbach
authors.forename: Sho
authors.initials: S
authors.lastname: Kabasawa
authors.forename: Izumi
authors.initials: I
authors.lastname: Kawasaki
authors.forename: Masataka
authors.initials: M
authors.lastname: Oosaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Iizuka
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Katayama
authors.forename: Takuya
authors.initials: T
authors.lastname: Awata
authors.forename: Shin
authors.initials: S
authors.lastname: Yoneya
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D007564:Japan; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016366:Open Reading Frames / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D022661:RNA, Untranslated / Q000235:genetics; D012307:Risk Factors; D012907:Smoking / Q000235:genetics*
chemical_list: C493495:CFH protein, human; D022661:RNA, Untranslated; D017242:Complement Factor H