Association of the hepatocyte growth factor gene with keratoconus in an Australian population

PLoS One. 2014 Jan 8;9(1):e84067. doi: 10.1371/journal.pone.0084067. eCollection 2014.

Abstract

Purpose: A previous study has indicated suggestive association of the hepatocyte growth factor (HGF) gene with Keratoconus. We wished to assess this association in an independent Caucasian cohort as well as assess its association with corneal curvature.

Participants: Keratoconus patients were recruited from private and public clinics in Melbourne, Australia. Non-keratoconic individuals were identified from the Genes in Myopia (GEM) study from Australia. A total of 830 individuals were used for the analysis including 157 keratoconic and 673 non keratoconic subjects.

Methods: Tag single nucleotide polymorphisms (tSNPs) were chosen to encompass the hepatocyte growth factor gene as well as 2 kb upstream of the start codon through to 2 kb downstream of the stop codon. Logistic and linear regression including age and gender as covariates were applied in statistical analysis with subsequent Bonferroni correction.

Results: Ten tSNPs were genotyped. Following statistical analysis and multiple testing correction, a statistically significant association was found for the tSNP rs2286194 {p = 1.1×10-(3) Odds Ratio 0.52, 95% CI--0.35, 0.77} for keratoconus. No association was found between the 10 tSNPs and corneal curvature.

Conclusions: These findings provide additional evidence of significant association of the HGF gene with Keratoconus. This association does not appear to act through the corneal curvature route.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Australia
  • Cohort Studies
  • Computer Simulation
  • Corneal Topography
  • Female
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Hepatocyte Growth Factor / genetics*
  • Humans
  • Keratoconus / genetics*
  • Logistic Models
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics

Substances

  • HGF protein, human
  • Hepatocyte Growth Factor

Grants and funding

This project was funded by the National Health and Medical Research Council (NHMRC) Clinical Research Excellence grant 529923 - Translational Clinical Research in Major Eye Diseases, NHMRC Senior Research Fellowship 1028444 (PNB) and the Angior Family Foundation. The Centre for Eye Research Australia (CERA) receives Operational Infrastructure Support from the Victorian Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.