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Title: Family-based association analysis of hepatocyte growth factor (HGF) gene polymorphisms in high myopia
Authors: Han, W
Yap, MKH 
Wang, J
Yip, SP 
Issue Date: 2006
Publisher: Association for Research in Vision and Ophthalmology
Source: Investigative ophthalmology and visual science, 2006, v. 47, no. 6, p. 2291-2299 How to cite?
Journal: Investigative ophthalmology and visual science 
Abstract: PURPOSE. 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] ≤ -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.
ISSN: 0146-0404
EISSN: 1552-5783
DOI: 10.1167/iovs.05-1344
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