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

¹From the Department of Ophthalmology, The First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou, China.; the ²School of Optometry, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China.; the ³Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China.

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.

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