title: Role of the hepatocyte growth factor gene in refractive error.
abstract: OBJECTIVE
  Refractive errors such as myopia and hypermetropia are among the leading causes of visual impairment worldwide. Several genetic loci have been associated with myopia but none to date have been reported for hypermetropia. We investigated the hepatocyte growth factor (HGF) as a candidate gene influencing these 2 refractive error states.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  A total of 551 individuals (193 males, 358 females; mean age, 55.41+/-12.65 years) including 117 individuals with high myopia <or= -6.00 diopters (D), 140 individuals with low/moderate myopia (-2.00 to -5.99 D), 148 emmetropic individuals (-0.50 to +0.75 D) and 146 hyperopic individuals (>+2.00 D) were included in the analysis from 3 different Australian population cohorts (The Genes in Myopia Study, the Blue Mountains Eye Study, and the Melbourne Visual impairment project).
  
  
  METHODS
  Genotyping of 9 tag single nucleotide polymorphisms (SNPs) that encompassed the entire HGF gene and its associated sequences as well as 6 additional SNPs identified through DNA resequencing was undertaken.
  
  
  METHODS
  Genetic association with refraction.
  
  
  RESULTS
  After correction for multiple testing, the SNPs rs12536657 (odds ratio [OR], 5.53; 95% confidence interval [CI], 1.14-26.76) and rs5745718 (OR, 2.24; 95% CI, 1.30-3.85) showed significant association with hypermetropia. Whereas the SNPs rs1743 (OR, 2.02; 95% CI, 1.19-3.43; P = .009), rs4732402 (OR, 2.03; 95% CI, 1.23-3.36; P = 0.005), rs12536657 (OR, 2.38; 95% CI, 1.40-4.05; P = 0.001), rs10272030 (OR, 2.22; 95% CI, 1.31-3.75; P = 0.003), and rs9642131 (OR, 2.44; 95% CI, 1.43-4.14; P = 0.001) showed significant association with low/moderate myopia.
  
  
  CONCLUSIONS
  These findings present the HGF gene as the first gene significantly associated with hypermetropia as well as providing evidence of significant association with myopia in a second ethnic population. In addition, it provides insights into the important biological mechanisms that regulate human ocular development (emmetropization), which are currently poorly understood.
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Australia.
authors.forename: Sundar
authors.initials: S
authors.lastname: Veerappan
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Pertile
authors.forename: Amirul F M
authors.initials: AF
authors.lastname: Islam
authors.forename: Maria
authors.initials: M
authors.lastname: Schäche
authors.forename: Christine Y
authors.initials: CY
authors.lastname: Chen
authors.forename: Paul
authors.initials: P
authors.lastname: Mitchell
authors.forename: Mohamed
authors.initials: M
authors.lastname: Dirani
authors.forename: Paul N
authors.initials: PN
authors.lastname: Baird
mesh_terms: D016022:Case-Control Studies; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005838:Genotype; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D006956:Hyperopia / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009216:Myopia / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D017931:DNA Primers; D017228:Hepatocyte Growth Factor