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
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.
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