Role of the Hepatocyte Growth Factor Gene in Refractive Error

doi:10.1016/j.ophtha.2009.07.002

Ophthalmology

Volume 117, Issue 2, February 2010, Pages 239-245.e2

https://doi.org/10.1016/j.ophtha.2009.07.002 Get rights and content

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.

Section snippets

Participants

Participants for this study were recruited through the GEM Study,39, 40 the Melbourne Visual Impairment Project,⁴¹ and the Blue Mountains Eye Study.⁴² All individuals underwent cycloplegic refraction after dilation with either 0.5% or 1% tropicamide as previously described. Spherical equivalent measures were used throughout this study.14, 41, 42, 43 For inclusion in this study a range of selection criteria were applied. We selected only those individuals with Anglo-Celtic ancestry with

Clinical Data on 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 D; mean age, 50.62±13.33 years), 140 individuals with low/moderate myopia (−2.00 to −5.99 D; mean age, 52.09±12.65 years), 148 emmetropic individuals (−0.50 to +0.75 D; mean age, 55.12±9.51 years) and 146 hyperopic individuals (> +2.00 D; mean age, 62.69±11.70 years) were included in the analysis. There were no significant differences in the proportions of men and

Discussion

We have identified SNPs in the HGF gene associated with the 2 principal types of refractive error, low/moderate myopia and hypermetropia. This seems to be the first study positively to identify a gene for hypermetropia. A single SNP rs3735520 in this gene was previously associated with myopia in a Chinese cohort with high-grade myopia. Although we were not able to replicate the finding of this particular myopia-associated SNP in our Caucasian population, we were able to demonstrate that other

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: 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.

View full text

Original articleRole of the Hepatocyte Growth Factor Gene in Refractive Error

Objective

Design

Participants

Methods

Main Outcome Measures

Results

Conclusions

Financial Disclosure(s)

Section snippets

Participants

Clinical Data on Participants

Discussion

Prog Retin Eye Res

Ophthalmology

Prog Retin Eye Res

Am J Ophthalmol

Ophthalmology

J Lab Clin Med

VISION 2020-the right to sight: from strategies to action

Am J Ophthalmol

Prevalence and risk factors of myopia in Victoria, Australia

Arch Ophthalmol

The Prevalence of refractive errors among adults in the United States, Western Europe, and Australia

Arch Ophthalmol

A synopsis of the prevalence rates and environmental risk factors for myopia

Clin Exp Optome

Prevalence of myopia in Taiwanese schoolchildren: 1983 to 2000

Ann Acad Med Singapore

Myopia and the urban environment: findings in a sample of 12-year-old Australian school children

Invest Ophthalmol Vis Sci

Nearwork in early-onset myopia

Invest Ophthalmol Vis Sci

The role of educational attainment in refraction: the Genes in Myopia (GEM) twin study

Invest Ophthalmol Vis Sci

IQ and the association with myopia in children

Invest Ophthalmol Vis Sci

Support for polygenic influences on ocular refractive error

Invest Ophthalmol Vis Sci

Evidence of shared genes in refraction and axial length: the Genes in Myopia (GEM) twin study

Invest Ophthalmol Vis Sci

Heritability of refractive error and ocular biometrics: the Genes in Myopia (GEM) twin study

Invest Ophthalmol Vis Sci

Heritability and shared environment estimates for myopia and associated ocular biometric traits: the Genes in Myopia (GEM) family study

Hum Genet

Ocular refraction: heritability and genome-wide search for eye morphometry traits in an isolated Sardinian population

Hum Gen

Parental myopia, near work, school achievement, and children's refractive error

Invest Ophthalmol Vis Sci

Impact of family history of high myopia on level and onset of myopia

Invest Ophthalmol Vis Sci

Impact of heredity in myopia

Hum Hered

Genes and environment in refractive error: the twin eye study

Invest Ophthalmol Vis Sci

Original article
Role of the Hepatocyte Growth Factor Gene in Refractive Error