Role of the Hepatocyte Growth Factor Gene in Refractive Error
Received 4 November 2008; received in revised form 1 July 2009; accepted 1 July 2009. published online 11 December 2009.
Objective
Refractive errors such as myopia and hypermetropia are among the leading causes of visual impairment worldwide. Several genetic loci have been associated with myopia but none to date have been reported for hypermetropia. We investigated the hepatocyte growth factor (HGF) as a candidate gene influencing these 2 refractive error states.
Design
Case-control study.
Participants
A total of 551 individuals (193 males, 358 females; mean age, 55.41±12.65 years) including 117 individuals with high myopia ≤ −6.00 diopters (D), 140 individuals with low/moderate myopia (−2.00 to −5.99 D), 148 emmetropic individuals (−0.50 to +0.75 D) and 146 hyperopic individuals (>+2.00 D) were included in the analysis from 3 different Australian population cohorts (The Genes in Myopia Study, the Blue Mountains Eye Study, and the Melbourne Visual impairment project).
Methods
Genotyping of 9 tag single nucleotide polymorphisms (SNPs) that encompassed the entire HGF gene and its associated sequences as well as 6 additional SNPs identified through DNA resequencing was undertaken.
Main Outcome Measures
Genetic association with refraction.
Results
After correction for multiple testing, the SNPs rs12536657 (odds ratio [OR], 5.53; 95% confidence interval [CI], 1.14–26.76) and rs5745718 (OR, 2.24; 95% CI, 1.30–3.85) showed significant association with hypermetropia. Whereas the SNPs rs1743 (OR, 2.02; 95% CI, 1.19–3.43; P = .009), rs4732402 (OR, 2.03; 95% CI, 1.23–3.36; P = 0.005), rs12536657 (OR, 2.38; 95% CI, 1.40–4.05; P = 0.001), rs10272030 (OR, 2.22; 95% CI, 1.31–3.75; P = 0.003), and rs9642131 (OR, 2.44; 95% CI, 1.43–4.14; P = 0.001) showed significant association with low/moderate myopia.
Conclusions
These findings present the HGF gene as the first gene significantly associated with hypermetropia as well as providing evidence of significant association with myopia in a second ethnic population. In addition, it provides insights into the important biological mechanisms that regulate human ocular development (emmetropization), which are currently poorly understood.
Financial Disclosure(s)
The authors have no proprietary or commercial interest in any of the materials discussed in this article.
Available online: December 11, 2009.
1Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Australia
2Vision Cooperative Research Centre, Sydney, Australia
3Centre for Vision Research, University of Sydney, Australia
Correspondence: Associate Professor Paul N. Baird, Centre for Eye Research Australia, The University of Melbourne, 32 Gisborne Street, East Melbourne, 3002, Australia
Manuscript no. 2008-1310.
Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.
Supported by the Australian Federal Government through the Cooperative Research Centres Program, the National Health and Medical Research Council of Australia, Joan and Peter Clemenger Trust, Helen Macpherson Smith Trust, L.E.W Carty Trust, Angior Family Foundation, the Myra Stoicesco Charitable Trust as administered by Equity Trustees Ltd and the Sunshine Foundation.
ABSTRACT