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 &amp Visual Science (Impact Factor: 3.66). 06/2006; 47(6):2291-9. DOI: 10.1167/iovs.05-1344
Source: PubMed

ABSTRACT 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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Aim: To investigate the association between high myopia (HM) and single nucleotide polymorphisms (SNPs) in the myocilin (MYOC), hepatocyte growth factor (HGF), hepatocyte growth factor receptor (MET), and aggrecan (ACAN) genes in a Han Chinese population. Methods: Sixteen SNPs were genotyped by the SNaPshot method in a subject group composed of 1052 HM patients and 1070 controls. Statistical analysis was performed to determine the association between the SNPs and the susceptibility of HM. Results: Two SNPs (rs3784757 and rs1516794) in ACAN were significantly associated with HM (p=0.0334 and 0.0236, odds ratio [OR]=0.83 and 0.79, respectively). The risk haplotype CA and the protective haplotype TT, generated by rs3784757 and rs1516794, showed significant association with HM (p=0.0327 and 0.0304, OR=1.21 and 0.80, respectively). Two SNPs (rs38857 and rs10215153) in MET and one SNP (rs3784757) in ACAN showed significant association with HM (p=0.0064, 0.0113, and 0.0373; OR=4.14, 5.74 and 0.52; respectively) of recessive model. None of the other SNPs showed significant association with HM. Conclusions: Our results suggested that genetic variants in ACAN and MET are associated with HM. Functional roles of ACAN and MET in the development of HM need to be further investigated.
    Genetic Testing and Molecular Biomarkers 04/2014; · 1.44 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Genome-wide association studies (GWAS) use high-throughput genotyping technologies to genotype thousands of single-nucleotide polymorphisms (SNPs) and relate them to the development of clinical and quantitative traits. Their use has been highly successful in the field of ophthalmology, and since the advent of GWAS in 2005, many genes not previously suspected of having a role in disease have been identified and the findings replicated. We conducted an extensive literature review and describe the concept, design, advantages, and limitations of GWAS and provide a detailed description of the applications and discoveries of GWAS in the field of eye disease to date. There have been many novel findings revealing previously unknown biological insights in a diverse range of common ocular conditions. GWAS have been a highly successful modality for investigating the pathogenesis of a wide variety of ophthalmic conditions. The insights gained into the pathogenesis of disease provide not only a better understanding of underlying disease mechanism but also offer a rationale for targeted treatment and preventative strategies. Expansive international collaboration and standardised phenotyping will permit the continued success of this investigative technique.Eye advance online publication, 27 June 2014; doi:10.1038/eye.2014.145.
    Eye (London, England) 06/2014; · 1.97 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: While myopia is an increasingly common refractive error worldwide, its prevalence is greatest in urbanized regions in east Asia. Myopia is a complex multifactorial ocular disorder governed by both genetic and environmental factors and possibly their interplay. Evidence for a genetic role in myopia has been derived from studies of syndromal myopia, familial correlation studies and linkage analyses. More recently, candidate gene and genome-wide association studies have been utilized. However, a high proportion of the heritability of myopia remains unexplained. Most genetic discoveries have been for high myopia, with the search for genes underpinning myopia of lesser severity yielding fewer positive associations. This may soon change with the use of next-generation sequencing, as well as the use of epigenetics and proteomic approaches.
    Expert Review of Ophthalmology 01/2014; 8(1).

Full-text (2 Sources)

Available from
May 22, 2014