Abstract
PurposeA 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.ParticipantsKeratoconus 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.MethodsTag 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.ResultsTen 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.ConclusionsThese 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.
Highlights
Keratoconus (KC) is a common corneal condition characterised by a progressive corneal thinning resulting in corneal protrusion, irregular astigmatism and decreased vision [1]
Following statistical analysis and multiple testing correction, a statistically significant association was found for the Tag single nucleotide polymorphisms (tSNPs) rs2286194 {p = 1.1610-3 Odds Ratio 0.52, 95% confidence intervals (95% CI) - 0.35, 0.77} for keratoconus
No association was found between the 10 tSNPs and corneal curvature
Summary
Keratoconus (KC) is a common corneal condition characterised by a progressive corneal thinning resulting in corneal protrusion, irregular astigmatism and decreased vision [1]. It accounts for some 31% of corneal grafts in Australia [2]. Other rare forms of surgical treatment include epikeratoplasty, photorefractive keratectomy, or intra corneal rings [3,4,5] All these techniques correct the refractive error of KC but do not treat the underlying cause of the corneal weakness and thinning, and cannot stop the progression of KC. Recent clinical trials using corneal cross linking, currently provide one of the best strategies to retard the progression of KC [6]
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