Family-Based Association Analysis of Hepatocyte Growth Factor ( HGF ) Gene Polymorphisms in High Myopia

Department of Ophthalmology, The First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou, China.
Investigative Ophthalmology & Visual Science (Impact Factor: 3.4). 06/2006; 47(6):2291-9. DOI: 10.1167/iovs.05-1344
Source: PubMed


To investigate the association of high myopia with polymorphisms in the hepatocyte growth factor (HGF) gene, a potential candidate for myopia development.
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).
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.
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.

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    • "Other studies have also reported positive associations with SNPs in HGF and mild/moderate myopia (rs3735520; Yanovitch et al., 2009). Additional SNPs in HGF have also been reported as positively associated with high myopia (rs2286194, rs3735520) in case–control cohorts of Caucasian and Chinese ethnicity, but the results in the Chinese cohort was not replicated in a second independent study (Han et al., 2006; Wang et al., 2009; Yanovitch et al., 2009). From these linkage, genome-wide association and candidate gene-based studies it is clear that Australian twins are a valuable resource for the discovery of novel genes and gene variants associated with ophthalmic traits. "
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    • "To date, over 20 genetic loci have been mapped using linkage analysis for both common myopia and high myopia [11-17]. A recent plethora of genome wide association studies have shown positive associations with refractive error [14,18-25]. Of late, large parallel sequencing techniques have been used to identify causal genes for ocular disorders including myopia. "
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    • "Vitreous chamber is the largest compartment in the eye, and its depth accounts for the largest proportion of axial length. These findings could explain the previous report of HGF as a high myopia-associated gene in the Chinese population [25]. Intriguingly, HGF exhibited significant interaction with another myopia-associated gene GJD2, which also contributed to the genetic association with axial length and vitreous chamber depth. "
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