title: Family-based association analysis of hepatocyte growth factor (HGF) gene polymorphisms in high myopia.
abstract: OBJECTIVE
  To investigate the association of high myopia with polymorphisms in the hepatocyte growth factor (HGF) gene, a potential candidate for myopia development.
  
  
  METHODS
  Single nucleotide polymorphisms (SNPs) were screened and identified in the HGF gene region with denaturing high-performance liquid chromatography, and their linkage disequilibrium pattern was established in a Han Chinese population (n=150). Tag SNPs were selected and genotyped using restriction digestion and fluorescence polarization assays for 128 nuclear families with 133 severely myopic (mean spherical equivalent [MSE]<or=-10.0 D) offspring. A family-based association study was performed using FBAT and GenAssoc (Cambridge University, Cambridge, UK).
  
  
  RESULTS
  Of three tag SNPs (HGF5-5b, HGFe9, and HGFe10b) selected for association study, HGF5-5b, located in the upstream region, was found to be associated with high myopia considered as a quantitative trait (MSE) in additive, dominant, and recessive models (P=0.0157, 0.0108, and 0.0108, respectively). The genotype relative risk was 2.19 for the genotype C/T, and 2.14 for T/T with reference to C/C of HGF5-5b. Significantly reduced transmission was demonstrated for the haplotypes C-A-C (HGF5-5b, HGFe9, and HGFe10b; P=0.0031) and C-A (HGF5-5b and HGFe9; P=0.0015) in the recessive model, whereas significantly increased transmission was found for haplotype T-C (HGF5-5b and HGFe10b; P=0.0040) under the dominant model. Preferential transmission of haplotypes remained significant even after correction for multiple comparisons. Analysis gave similar results, with myopia considered to be a qualitative trait.
  
  
  CONCLUSIONS
  HGF is a potential locus associated with high myopia in the Han Chinese population. This is the first study reporting the association of an HGF gene polymorphism with high myopia.
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou, China. hanweidr@hotmail.com
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.forename: Maurice K H
authors.initials: MK
authors.lastname: Yap
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Shea Ping
authors.initials: SP
authors.lastname: Yip
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid; D005192:Family Health; D005260:Female; D005454:Fluorescence Polarization; D005838:Genotype; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D047728:Myopia, Degenerative / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
chemical_list: C066855:HGF protein, human; D017228:Hepatocyte Growth Factor